Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more here...

The Revised Authoritative Guide To Vaccine Legal Exemptions Summary


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Vaccination of kittens

The aim of kitten vaccinations is to provide active, vaccine-derived immunity as early as possible. However, maternally derived antibody (MDA), which is essentially colostrally derived in kittens, may interfere with effective vaccination. As MDA declines, kittens may become susceptible to infection before they are responsive to vaccination, leaving an immunity gap (Figure 2.1). Some vaccines are better at overcoming MDA than others classically, intranasal vaccines are not interfered with by levels of antibodies that would interfere with systemic vaccines. However, with improvements in vaccines including newer types of adjuvant, other vaccines may also induce protection in the presence of low levels of MDA. an accurate timing of first vaccination is required, although in practice this is rarely done. In some situations earlier vaccination schedules may be appropriate, for example where there is a high risk of disease or where kittens are deprived of colostrum and therefore more likely...

Vaccination of adutt cats

In previously unvaccinated cats, or animals of unknown vaccination history, a primary vaccination course of two doses 3-4 weeks apart should be undertaken. In cats vaccinated as kittens, the first booster at 1 year of age is important in case the first vaccination course was ineffective (e.g. if MDA was still at interfering levels). The onset of immunity is 7-10 days after systemic vaccination and 2-4 days after an intranasal vaccine. Although annual boosters are generally recommended for all injectable vaccines, there is some evidence that for panleucopenia the duration of immunity may be longer, up to several years (Gaskell et al, 2002a, b). However, clearly a number of variables may influence this, including the potency of the actual product. For feline herpesvirus and feline calicivirus, although immunity may again last for up to several years, it is only partial in most animals (Scott & Geissinger, 1997, 1999). For feline leukaemia, there is limited evidence that, after natural...

Rational vaccine design

Ideally, an attenuated organism would possess the ability to replicate vigorously and induce an immune response, while being completely devoid of virulent properties. Strains with hyperattenuation (reduced vitality) and substantial or unstable residual virulence are unacceptable for use as vaccines. A knowledge of the genetic basis of virulence allows us to target virulence determinants and to create strains lacking the genes required for pathogenicity. Another challenge in vaccine development arises when dealing with viruses that have a very high rate of antigenic drift, e.g. influenza. In this case, standardized tech niques for virus attenuation would be desirable in order to prepare vaccines with consistent effectiveness against the new influenza strains that emerge each year. It was found that passaging influenza virus at low temperatures results in attenuation and that the determinants of attenuation are located on the PA, M, PB2, and PB1 genes of the cold-adapted influenza A...

Attenuated organisms versus killed vaccines

Arguments about the relative advantages of live and killed vaccines are endless and started with the invention of vaccines themselves. Live vaccines are generally less stable than killed vaccines and require freezing during transportation and storage. The possibility of contamination with live adventitious agents, including the unknown ones, is a consideration that is hard to discount. But the greatest shortcoming of live vaccines is their potential for reversion to virulence. Because of this, in the nineteenth century, variolation was considered a felony in England. Modern vaccines, especially the ones created with a knowledge of the molecular basis of virulence, are much safer than the attenuated strains of the past. In addition, sophisticated methods of quality control are now used to ensure the safety of live vaccines. The advantages of using attenuated organisms as vaccines are numerous. Since they replicate in the body of a vaccinee, the dose of a live vaccine is usually small,...

Acquired immunity vaccines

The polypeptide capsule of B. anthracis is only weakly antigenic and there is little evidence to suggest it contributes to naturally acquired immunity or can produce artificially induced protection against anthrax. Pasteur derived his vaccine strains by sub-culturing at 42 43 C and was inadvertently curing the bacilli of pXOl. However, cap+ tox strains are, in fact, not protective and both the partial efficacy and the residual virulence of Pasteur's vaccines are now explained in terms of mixed cultures with residual uncured forms. Cap tox+ strains of B. anthracis are protective and one such strain, produced by Sterne in 1937, has remained to this day the basis of a highly successful live-spore animal vaccine, although this vaccine too retains some residual virulence in certain susceptible species (albeit considerably less than wild type tox+ cap+ B. anthracis), such as guinea pigs, a number of inbred strains of mice and certain livestock species, notably goats and llamas. As a result...

Vaccination schedules

Most data sheets recommend primary vaccination for kittens followed by annual boosters thereafter. Such regimens maximise protection for the individual and are generally based on both experimental challenge studies and field data provided by the manufacturer. However, in recent years there has been considerable discussion as to whether such schedules are always appropriate, largely because of concerns about possible safety issues. These issues have been particularly highlighted by the increasing use of inactivated adjuvanted vaccines in cats, and the possible association between such vaccines and the formation of vaccine-associated sarcomas. Because of these concerns, some authorities in the USA have designated certain vaccines as 'core' vaccines, such that all animals should undergo primary vaccination as indicated by the manufacturer, followed by revaccination 1 year later and then boosters every 3 years. A vaccine is designated as core either if the consequences of infection are...

TABLE 1413 Type of Treatment and Regimen for Rabies Postexposure Prophylaxis by Vaccination Status

HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to provide immediate antibodies until the patient responds to rabies vaccine by producing antibodies. Failure to use HRIG has led to rabies, despite appropriate postexposure prophylaxis with human diploid cell vaccine. If HRIG was not given when vaccination was begun, it can be given through the seventh day after administration of the vaccine.19 Beyond the seventh day, HRIG is not indicated because an antibody response is presumed to have occurred. The CDC recommends that as much as possible of the full dose be infiltrated around the wound. 22 HRIG should never be administered in the same syringe or into the same anatomic site as the vaccine. Even if the wound has to be sutured, it should be infiltrated locally with HRIG. This practice is safe and does not create an additional risk of infection. 25 However, caution is needed when injecting into a tissue compartment, such as the finger pulp, because...

Post Vaccination Testing

Many preventive vaccines function by stimulating the development ofneutralizing antibodies to the immunogen(s), these antibodies being sufficient to protect against a subsequent infection by the pathogen. These vaccines are designed to induce a humoral or B-cell response that translates into an enduring production of protective, high-affinity, neutralizing antibodies against the pathogen 23 . The measurement of these specific antibodies in serum can be directly correlated with the efficacy of a vaccine to provide immunity against distinct pathogens 24 . Traditionally, such measurements are made by immunoassays, with no requirements for cell-based assays. However, B-cell vaccination strategies do not provide effective immunity against all pathogens, especially against rapidly mutating viruses, bacteria, and parasites. The control and elimination of these pathogens is subject to the effectiveness of the infected host's T-cell responses and cellular immune mechanisms. For all vaccines,...

Analytical Assays And Quality Control Of Excipients For Vaccine Formulations

Any excipient for a vaccine formulation is treated as a component of a parenteral formulation and must adhere to strict FDA requirements of compliance and regulation of these materials. Most of the excipients commonly used in vaccine formulations (except adjuvants) are also used in many other parenteral formulations and thus have a long safety and tolerability profile. Many components like the adjuvants have to have established guidelines for purity, monomer ratios, and concentrations. Ideally, purity greater than 98 is considered as the minimal criterion. The selection of concentration is based on extensive preclinical evaluation to show minimum reacto-genicity and enhanced immunogenicity. Typical assays used for quantifying the excipients are based on reversed phase-high performance liquid chromatography, Table 5 A Representative List of Excipients Currently Under Evaluation in New Vaccine Formulations Table 5 A Representative List of Excipients Currently Under Evaluation in New...

Selection Of Excipients For Next Generation Vaccines

Next generation vaccine formulations will comprise several antigens that will include glycoconjugates, recombinant proteins, plasmids, oligonucleotides, peptides and additional adjuvant molecules for enhanced immunogenicity. These complex formulations will need a rational selection of stabilizers, preservatives, and buffers. Most paramount in this selection is that the stability of all components of the vaccine should be such that the potency of the final formulation is maintained. Enhanced shelf life is another parameter that would dictate formulation development in vaccines. New vaccine modalities such as DNA vaccines are currently being explored using charged PLG microparticles (21) as delivery systems. These and similar novel delivery technologies will be essential components of some of the next generation vaccines.

Early investigation of the HIV envelope as a vaccine target identified peptide inhibitors of HIV infection

Initial efforts in the search for a vaccine to prevent HIV infection centered on the HIV envelope glycoprotein gp160 as a target for neutralizing antibodies 7-10 . The HIV envelope glycoprotein is a type I integral membrane protein translated as a polyprotein that is subsequently cleaved to yield the gp120 surface subunit and the gp41 transmembrane subunit, which associate as non-covalently bound oligomeric trimers on the surface of virions 11-15 . The process of HIV binding and entry into CD4+ target cells involves several discrete and discernable steps leading to a series of conformational changes in both envelope subunits. The first step is the binding of the virus envelope via the gp120 subunit to the CD4 receptor on the target cell surface. This interaction leads to conformational changes in the gp120 subunit that exposes and creates a binding site for a chemokine coreceptor. The major coreceptors for HIV are the CCR5 and CXCR4 coreceptor, and the presence of one or both of these...

Advantages of DNA Vaccines

DNA vaccines represent a new approach to immunization, in that an individual is directly inoculated (injected) with DNA that genetically encodes one or more of the antigens associated with the infectious agent. In effect, the recipient of a DNA vaccine produces the immunizing protein (antigen) within his own cells as a result of the immunization process. This revolutionary approach to vaccination offers many advantages over conventional vaccines. A major advantage is that DNA vaccination stimulates both the antibody and cell-mediated components of the immune system, whereas conventional protein vaccines usually stimulate only the antibody response. Furthermore, DNA vaccines are simpler to produce and store than conventional vaccines, and are therefore less expensive. Preliminary studies to date indicate that DNA vaccines appear to be very safe and to produce no side effects.

DNA Vaccination Techniques

DNA vaccination involves immunization with a circular piece of DNA, known as a plasmid, that contains the gene (or genes) that code for an In many respects, this process is reminiscent of what occurs during a viral infection, when viral proteins are expressed within host cells. Thus, a DNA vaccine is somewhat like a very simple, nonreplicating virus. However, plasmid DNA vaccines do not replicate within the host, and therefore do not infect neighboring cells, as occurs during a viral infection. This innovation in vaccination strategy was discovered some years ago, but the active development of this technology only began after Stephen Johnston's group at the University of Texas Southwestern Medical Center demonstrated that plasmid DNA can induce the formation of antibodies against an encoded protein in 1992. Johnston's group was able to show that when mice are innoculated with plasmid DNA encoding human growth hormone, the mice produce antibodies against the hormone. There are two...

Immunological requirements expectations of a vaccine

Vaccines may be administered to populations where the disease is endemic and a recipient already infected. Both specific and nonspecific immune responses may then have a therapeutic effect and contribute to the control of an existing infection. In most situations, however, vaccination is planned to protect from an infectious agent to which the recipient may be exposed at some variable time in the future. In this case, the requirements differ and depend entirely on the specific components. Because the life of naive lymphocytes is quite short (from days to a couple of weeks), a vaccine should 1) generate a large pool of memory T and B cells 2) cause antigen to persist as antigen antibody complexes on follicular dendritic cells so that memory B cells are formed and constantly recruited to become antibody-secreting cells and thus provide a continuing supply of antibody of increasing affinity and 3) provide appropriate T cell epitopes to overcome the genetic restriction to this response in...

Vaccines Adverse Reactions To

Vaccines developed from the need to prevent the continuing morbidity and mortality from infectious diseases. The earlier attempts included variolation, the practice of deliberately inducing disease by transmission of material from smallpox pus or scabs which was practised in China and India and spread to the Middle East and thence to Europe and America. Despite the high risk of variolation (0.2-2 mortality), it was much less than the risk of death from being infected during a smallpox epidemic. Benjamin Franklin stated in his autobiography, 'In 1736, I lost one of my sons (Francis Folger), a fine boy of four years old by the smallpox. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of parents, who omit the operation on the supposition that they should never forgive themselves if a child died under it my example shows the regret may be the same either way, and that therefore the safer should be chosen.' The history...

Bordetella pertussis vaccination

The whole-cell (inactivated) pertussis vaccine is the most reactive component of the triple antigen diph-theria-tetanus-pertussis (DTP) vaccine. Several categories of reaction are recognized. Some of these, like protracted bouts of crying with unusual shock-like states or minor local and systemic effects, do not have long-term consequences. Another category includes more major neurological reactions which may lead to permanent disability. It has been extraordinarily difficult to establish a causal relationship between such injuries and vaccination. For example, the frequency of encephalopathy with residual brain damage one year after DTP administration was estimated to be 1 300 000 cases, but the correct figure could be between 1 54 000 and 1 5 300 000 cases. A study by the Institute of Medicine (lOM) in the USA concluded that the pertussis component of DTP is responsible for rare instances of encephalopathy, but not for other disabling effects. Some countries stopped vaccination with...

Other childhood vaccines

More recently, the IOM has published findings on adverse events associated with a number of other childhood vaccines, to see whether any evidence bearing on causality could be established. Reactions to the diphtheria and tetanus toxoids, measles, mumps, polio, hepatitis B, and Haemophilus influenzae type B (Hib) vaccines, were examined. Evidence for neurological disorders (both demyelinating and nondemyelinating diseases) and a series of immunologic reactions (anaphylaxis, Arthus reaction, delayed-type hypersensitivity and autoimmunity in particular) was sought. After an exhaustive review of the available data, the findings suggested that these vaccines are remarkably safe. Table 1 Reported cases (deaths) per million in the United States following smallpox vaccination Primary vaccination (5959000)

Groups at risk from vaccination

Certain groups have a higher morbidity and mortality rate to natural infections compared to the normal population. This includes diabetics (influenza and pneumococcal pneumonia), immunocompromised or immunodeficient people. Pregnant women represent a special case because of the potential harm to the embryo. Live agent vaccines should be withheld from such groups. On the other hand, maternal immunization to protect the fetus and mother from certain diseases, e.g. tetanus, is the aim of the World Health Organization. As vaccine development becomes more highly specialized with the great potential for peptide and sub-unit preparations, for recombinant live vectors and for direct immunization with nucleic acids, the risk of side-effects following vaccination should decrease. It may never be possible however to completely eliminate all hazards but these are likely to occur at such a low frequency that they are detectable only after mass immunizations. Though society in the long run must...

Vaccine development

No effective cholera vaccine has yet been put into widespread use. Immunity to cholera can occur in the absence of antibodies to CT, but experimental studies suggest that antibacterial and antitoxic immunities can act in synergy. A vaccine based on killed whole cells and purified CT B subunit has shown promise in extensive field trials in Bangladesh and elsewhere, but the presence of B subunit in the preparation only seems to be important for immunity in the first year or two. proportion of volunteers. This is in part correlated with the colonizing potential of the vaccine strain. One construct, CVD103HgR, based upon a poorly colonizing strain in which ctxA has been deleted, as well as several other modifications, seems to be efficacious and is being evaluated in the field. There is also considerable variation in the success of this approach and this again appears to be strain-dependent, as was observed with 0139 strains into which the same mutations were introduced. A further...

Live attenuated vaccines

One of the limitations of non-living vaccines, including both conventional killed vaccines and subunit vaccines, is that the protective effect on initial immunization can be relatively poor and short-lived. Boosters are commonly needed, but even so the protection is usually inferior to that conferred by a live vaccine. The conventional route for development of a live attenuated vaccine involves repeated laboratory subculture, especially under non-favourable conditions. For example, a virus may be repeatedly cultured using a cell line that is a poor host for the wild virus, or a bacterium may be repeatedly grown using a medium in which the pathogen grows very weakly. The TB vaccine BCG was developed by repeated subculture on potato slices soaked in glycerol and ox bile over some 20 years. The principle is that as the pathogen adapts to these unusual conditions it will at the same time lose the ability to infect human or animal hosts. The only way of testing this is to examine the...

Current Knowledge on TCell Responses in Vaccine Trials

Knowledge gained from analyzing T-cell responses in natural infections, as in HIV-1 infection previously described (above), has provided valuable insights into what is needed for vaccine design and vaccination schedules. Today, novel technological advances are being made, leading in turn to improved ways of measuring CD8+ T-cell responses. Increasingly, these responses are being tested for in animal models and clinical trials of new vaccines. Against HIV infection, much of the recent effort to derive efficacious prophylactic vaccines has focused on the design and development of recombinant poxviral- and adenoviral-vector vaccines. These have been used either singly or together, or in combination with plasmid DNA vaccines in prime-boost regimes 95, 118 . For example, many clinical trials have already been conducted in volunteers (total over 1800) with ALVAC candidate prophylactic vaccines. The latter are usually designed to express multiple HIV antigens, including gp120, gag, and pro...

Vaccination Programs their Culture and Context

Global policy-making processes have been studied more by medical historians and health policy scientists than by medical anthropologists. Medical anthropologists have focused on the implementation of immunization programs and the acceptability of vaccines in diverse socio-cultural settings. They have shown how at the local level immunization programs are characterized by a target-oriented approach and emphasis on strict adherence to vaccination rules and procedures that have been developed in an international setting (Banjeri, 1990). Usually, the organizational culture of vaccination programs combines an emphasis on strict adherence to many rules with strong social control through monitoring of the achievement of targets (Nichter, 1990 Onta, Sabroe, & Hansen, 1998 Streefland, 1989). Onta et al. (1998) report that Primary Health Care Service Outlets (PHSOs) and the district health office in Nepal responded to the target-orientation by exaggerating coverage. The PHSOs reported numbers...

Resistance to Vaccination Regimes

When vaccination was introduced by colonial governments in the last century resistance was a rather common response. Presently, collective resistance occurs for religious reasons when parents reject protection through vaccination because they consider this unjustified interference with God's will or because their explanatory model of how a child ought to gain resistance against a disease is at odds with the biomedical model. Collective resistance may also occur when the population distrusts the state (Streefland, 2001), when the media report adverse effects or undisclosed aims (e.g., sterilization of pregnant women by way of the TT vaccination). A survey on the acceptance of vaccination among different ethnic groups in the Netherlands found more informed resistance among highly educated white populations (Hardon, Streefland, Egers, & Gerrits, 1998). Reasons for non-acceptance are the belief that childhood illnesses play a role in the development of children. Parents specifically...

Live recombinant vaccines

Live Recombinant Vaccines

One of the novel advances in vaccine technology that has been made possible by genetic manipulation is the construction of vaccines that confer immunity to several diseases simultaneously. This can be achieved by inserting the genes for key antigens from different pathogens into a single live vaccine. Much of this work has been carried out using the vaccinia virus (the smallpox vaccine) as the carrier. Vaccinia is a rather large and inconvenient virus to use for genetic manipulation (with a genome size of 187 kb), and the insertion of genes requires the use of in vivo recombination. This is shown schematically in Figure 16.3. The required gene is inserted into an E. coli vector, adjacent to a promoter derived from vaccinia. This plasmid also carries a defective thym-idine kinase (TK) gene from vaccinia, interrupted by the promoter and the cloning site. If an animal cell is infected with vaccinia virus, and at the same time transformed with the recombinant plasmid, the homology between...

Immunity and Vaccination

Acquiring immunity through vaccination has played a major role in the control of a variety of diseases, particularly viral infections that are otherwise untreatable. This involves exposing a person to a material that will stimulate immunity to a particular agent. The material used may be a killed, inactivated, or weakened strain of the agent, a portion of its surface, one of its products, or a closely related agent. One of the greatest successes of vaccination has been with smallpox. This once devastating disease killed millions in the Old World and scarred countless others. It was then brought to the New World, where it killed millions of Native Americans, in some cases wiping out entire cultures. In fact, the infection was spread intentionally to some tribes by European invaders who distributed infected blankets (an early example of biological warfare). Vaccination with material from the pustules (pox) of victims was practiced in Asia for at least several centuries, but sometimes...

Recombinant vaccines expressing tumor associated antigens

The immunogenic nature of CEA in humans is unclear, and the induction of T cell responses with protein vaccination is weak. Therefore, co-presentation of CEA with a strong immunogen such as a virus might increase its immuno-genicity and induce strong anti-CEA immune responses 23 . Vaccinia viruses are highly immunogenic and stimulate both humoral and cellular mediated immune responses. In a Phase I trial immunization with a CEA-encoding recombinant vaccinia (rV-CEA) was investigated over a limited dose range 24 . Toxicity was limited to modest local inflammation at the inoculation site as well as low grade fever and fatigue. Unfortunately, there was no evidence of CEA-specific T cell proliferation, antibody responses or DTH responses. The fact that patients were treated with only two vaccinations may explain the absence of specific immune activation. Because vaccinia virus proteins are highly immunogenic, vaccinia recombinants can only be administered once or twice due to the...

Immune globulin and vaccines

A live attenuated varicella vaccine was developed in the 1970s and is currently licensed in Japan, Europe and the USA. The vaccine virus was designated Oka strain after the name of the 3-year-old boy with chickenpox from whom it was isolated. The first human studies of the VZV vaccine were carried out in Japan with subsequent clinical trials in Europe and the US. Because of their increased susceptibility to severe complications of chickenpox, the initial recipients of the vaccine were children with leukemia. Initially, one vaccination was given. However, because of low seroconversion rates the number of vaccine doses was raised to two injections. Under the latter regimen, 95 of vaccine recipients developed antibody 66 remained seropositive 3 years after immunization. A small number of vaccine recipients have developed clinical chickenpox after exposure in the community this disease is called 'breakthrough chickenpox'. Usually the disease has been mild. Based on efficacy data derived...

Newer approaches to vaccine development

There are a great variety of diseases - viral, bacterial and parasitic - for which no vaccines are available. The need is great five parasitic diseases alone affect about one-quarter of the world's population. Reasons such as the inability to grow sufficient of the organism either in vitro or in an animal, the complex nature of the infectious process (often including substantial suppressor effects), a lack of understanding of the basis of many chronic and persisting infections, all contribute to the lack of progress in vaccine development. Fortunately, techniques have become available which may overcome some of these restrictions. In association with class I or II MHC antigens, specific linear amino acid sequences from foreign proteins may be recognized by the T cell receptor (TCR). By using a sufficient range of such sequences most people in an outbred population should respond. Peptide-based vaccines provide the opportunity to eliminate sequences which may cause immunosuppression or...

Conclusion Genomics And Vaccination

Despite the advances associated with molecular techniques, meningococcal disease remains a globally significant health problem, and the prospect of comprehensive vaccination remains elusive. Whereas vaccines based on the capsular polysaccharide are either licensed or under development against meningococci associated with serogroups A, C, and Y, as well as W-135, attempts to develop a polysaccharide-based serogroup B vaccine have proven unsuccessful. This fact is especially relevant as much of the meningococcal disease in Europe and North America is caused by meningococci associated with the serogroup B capsule. A number of alternative approaches to the development of serogroup B meningo-coccal vaccines are currently in development, 14 and these are summarized in Table 1. The recent completion of three meningococcal genomes (http www.sanger. Projects N_menigitidis ) Refs. 23,24 has revolutionized the process of vaccine development and the application of genomic approaches such as...

Plasmodium falciparum from genomic sequence to vaccines and drugs

Tabelas Gravidez Precoce

Malaria parasites infect 300-500 million and kill 1.5-2.7 million people annually. In areas with intense transmission, each infected individual may harbour more than five different strains of Plasmodium falciparum. There is now a major international effort to sequence the 30 megabase genome of P. falciparum. Initially there was scepticism within the field that the genome could be sequenced completely. This was in large part due to the instability of the DNA in Escherichia coli, a phenomenon thought to be at least in part due to the high (80.2 ) A+T content of the genome. With the publication of the 947 kb sequence of chromosome 2 of P. falciparum (Gardner et al 1998), the capacity to sequence the genome has been established, and there is great hope that elucidation of the sequence of the estimated 6000 genes on 14 chromosomes will lead to increased understanding of the biology of the parasite and then to the development of new drugs to treat and prevent the disease and vaccines that...

Attenuated Organisms As Vaccines

Attenuation is a process of genetic changes leading to a loss of virulence by pathogenic microorganisms while retaining the capacity to induce an immune response in susceptible hosts, resulting in lasting protection from a disease. Attenuation is a part of the natural evolution of pathogenic microorganisms, and is used by man to create 'live' vaccines against infectious diseases (Table 1), in contrast to 'killed' vaccines consisting of inactivated pathogens or their immunogenic subunits. Both types of vaccines have advantages and shortcomings these will be compared after a brief historical overview and discussion of the general principles behind the process of attenuation. The evolution of pathogens involves several concurrent trends, including immunological drift to escape host defense mechanisms, expansion into new populations (including cross-species adaptation), acquiring new pathogenic factors and properties, and, finally, reduction and loss of pathogenicity (attenuation). While...

Vaccination therapies

Vaccination differs from nonspecific immune-based therapies in that the goal is not general but rather specific activation of the immune system to eliminate tumor cells without affecting surrounding normal tissue 4 . It is generally assumed that specific vaccination should result in activation of the two main arms of the immune system, namely the humoral (antibody producing B cells) and the cellular immune response (T cells) 5, 6 . B cells recognize the tumor antigens in their native protein state at the cell surface, whereas T lymphocytes recognize proteins as peptide fragments, presented in the context of major his-tocompatibility complex (MHC) antigens on the surface of the tumor cells. There are two types of T cells, CD4 and CD8, which recognize antigens through a specific T cell receptor. These antigens are presented by a group of specialized cells called antigen-presenting cells (APC). A variety of cells are capable in processing and presenting antigens including B cells,...

The HIV vaccine challenge

The principle of vaccination is straightforward the inoculation of a safe antigen to induce an immune response against the etiological agent of an infectious disease and in doing so confer protection to subsequent infection. Successful vaccines currently available against virus-induced diseases include live attenuated strains that produce infection without inducing disease, such as the Sabin polio vaccine. Such strategies are not practically applicable to HiV-1 because the safety of attenuated strains cannot be evaluated before use. Even extensive genetic modification (e.g. deletion of regulatory genes critical for virus replication) would not necessarily ensure against reversion of the virus to virulence. While this strategy of vaccination with mutants deleted of key regulatory genes protected adult macaques from experimental SIV challenge, it proved fatal to immunocompromised neonatal animals. An alternative strategy is the subunit vaccine which has already proved successful for...

Antiidiotype antibody vaccines

The murine monoclonal antibody CEA Vac mimics a highly restricted CEA epitope that has no cross-reactivity with CEA expressed by normal human tissues. This antibody acts as a surrogate tumor antigen, inducing anti-CEA antibody responses and specific T cell responses, and was demonstrated to have a major antitumor effect in a murine tumor model 20 . In a study in 23 patients with advanced colorectal cancer, 17 generated anti-anti-idiotype responses, and 13 of these were proven to be true anti-CEA responses 21 . However, none of the patients had objective clinical responses and toxicity was limited to local swelling and minimal pain at vaccination site. CEA Vac has also been evaluated in the setting of adjuvant therapy of high risk colorectal cancer 22 . 32 patients were included in this study, 4 stage II, 11 stage III, 11 completed resected stage IV and nine stage IV patients with minimal residual disease. 15 patients received 5-FU-based chemotherapy, simultaneously with the CEA Vac....

Vaccination and immunotherapy

The development of vaccines against the important systemic fungal infections is under intense investigation. A vaccine consisting of formaldehyde-killed spherules of C. immitis was protective in a mouse model of coccidioidomycosis, but no efficacy was demonstrated in a large trial of susceptible persons in the endemic area. Local reactions limited the dose that could be given. Immunization with subcellular fractions or purified antigens is likely to be better tolerated and suitable antigens are under development for both C. immitis and H. capsulatum. Cypto-coccal glucuronoxylomannan, the major component of the polysaccharide capsule of C. neoformans, has been linked to tetanus toxoid and used to immunize mice. Conjugation with tetanus toxoid enhanced immunogenicity and conferred T cell-dependent properties to glucuronoxylomannan.


Historically, the development of Ad vaccines provided new insights into important issues regarding the determination of the safety and efficacy of live viruses for disease prophylaxis. The development of an Ad vaccine became a major priority in the early 1960s after the realization that Ads were responsible for most of the ARDs in up to 80 of American military recruits (who often required hospitalization). Types 3, 4, 7, 14, and 21 Ads caused most of the disease in military recruits and trials of the first vaccines took place between 1958 and 1962. The initial vaccines consisted of inactivated whole-virus strains. However, besides not being completely effective, it was discovered that the seed stocks of vaccine virus were contaminated with fully viable SV40 as noted above. SV40 actually functioned as a helper virus that was essential for the replication of both Ad4 and Ad7. It was realized then that Ad grew in monkey kidney tissue culture only because many of these cells were...

Types of vaccine

Cat vaccines generally comprise either modified live, or inactivated (killed) adjuvanted vaccines administered subcutaneously ( Table 2.1). Modified live vaccines have been attenuated or altered to eliminate or reduce their virulence. Attenuation can be achieved in a number of ways, including serial passage in cell culture in the laboratory or by genetic manipulation, or by the choice of a naturally occurring apathogenic strain. Live vaccines have the disadvantage of an increased possibility of causing disease and also the potential of reversion to virulence. In traditional killed vaccines the whole agent has been inactivated chemically, whereas in subunit vaccines the agent has been dissembled and only certain parts are incorporated into the vaccine. Both traditional and subunit killed vaccines contain adjuvants to increase the immunogenicity of the vaccine. More recently, genetically engineered subunit vaccines have recently been produced for feline leukaemia virus vaccines where...


Currently, it is not possible to induce complete host-protective immunity against infection with taeniid cestodes in dogs. Reports on induced immunity against E. granulosus in dogs are contradictory. Vaccination studies using somatic or in vitro products of protoscoleces, hydatid cyst fluid or somatic preparations of whole worms induce partial protection against infection in some dogs. Oncospheres of E. granulosus have been shown to be a potent source of host-protective antigens in sheep. Using recombinant DNA methods, antigen has been expressed in Escherichia coli and used to vaccinate sheep, inducing high levels of protection ( ) against experimental infection with E. granulosus. Use of a successful recombinant vaccine capable of protecting sheep against infection will be a useful new strategy for the control of hydatid disease in domestic livestock and potentially also in humans. However, before a recombinant vaccine can be used effectively in programs to control E. granulosus,...

Pneumococcal Vaccine

The seven-valent conjugated pneumococcal vaccine (Prevnar) was licensed in January 2000 and became incorporated in the standard recommendations for immunizations for infants in the United States. There is a dosage schedule for administration of this vaccine to children older than 24 months and younger than 5 years. Twenty-three-valent pneumococcal vaccine (Pneumovax) should be considered for individuals older than 5 years. These vaccines prevent serious bacterial infections that can affect the ears, nose, and throat as well as causing pneumonia.

Virus vaccines

Smallpox, once the scourge of millions, was in 1979 the first infectious disease to be declared successfully eradicated. This followed a worldwide campaign of vaccination by the World Health Organisation over the previous decade, and was made feasible by the fact that humans are the only reservoir for the virus. Vaccination is a preventative strategy that aims to stimulate the host immune system, by exposing it to the infectious agent in question in an inactivated or incomplete form. There are four main classes of virus vaccines Attenuated ( 'weakened') vaccines contain 'live' viruses, but ones whose pathogenic-ity has been greatly reduced. The aim is to mimic an infection in order to stimulate an immune response, but without bringing about the disease itself. A famous example of this type of vaccine is the polio vaccine developed by Albert Sabin in the 1960s. The cowpox virus used by Edward Jenner in his pioneering vaccination work in the late 18th century was a naturally occurring...

BCG vaccination

Prevention of active TB has focused on two strategies vaccination of children with bacilli Calmette-Guerin (BCG), and tuberculin skin testing followed by treatment of LTBI. Childhood immunization with BCG has been studied in three separate meta-analyses, which pooled both randomized controlled trials and case-control studies.81-83 BCG was shown to reduce miliary and meningeal TB by 75-86 , and pulmonary TB in children by 50 . However, great variation in efficacy was seen in different trials, and explained in part by distance from the equator.84 The disadvantages of routine BCG vaccination include false-positive tuberculin skin tests (see below), which compromises contact tracing and initiation of INH treatment of LTBI cutaneous abscesses and occasional disseminated BCG.

Subunit Vaccines

Recent studies using mutant strains of T. gondii indicate that the persistence of live organisms in the host is not necessary for the maintenance of protective immunity (10). If the antigens that stimulate the protective response can be identified, cloned, and properly expressed in vectors, the expressed proteins can be tested as candidates for vaccination. The genes for two other major proteins, the P14 surface antigen and the P28 cytoplasmic antigen, have also been cloned and expressed in vectors. These fusion proteins are being tested as immunogens for possible inclusion in a Toxoplasma vaccine (10,11).

T cell vaccines

It seems that T cells do not perform well as vaccines unless the cells have been activated. To be activated, the T cells are incubated for a minimum of about 6-8 h with their specific antigen, or with a T cell mitogen together with antigen-presenting cells. The molecular changes induced by activation that are critical for TCV have not been identified, but their effect is marked. Treatment of whole T cells with chemical cross-linkers can also enhance the effectiveness of some bur not all T cell vaccines. The T cell receptor (TCR) is clearly an important actor in TCV. Peptides of two different domains of the TCR have been found to mimic some of the effects of whole T cells as vaccines TCR V region peptides and TCR joining region peptides. The joining regions of the TCR (VDJ(3 and VJoO determine the epitopes that can be recognized by the particular TCR the joining regions also create the T cell idiotype. Thus, the response ro vaccination with a TCR joining region peptide is an...

Classic Vaccines

One of the greatest achievements in the history of medicine has been the development of vaccination. The use of vaccines has saved more lives than all other medical procedures combined, and represents one of the highest points in civilization's technical accomplishments. Vaccines are used to mobilize the immune system to prevent or combat infectious disease caused by exposure to viruses, bacteria, or parasites. A vaccine works by mimicking an infectious agent and inducing a protective immune response in the host, without actually causing the disease. Successful vaccination provides protection for individuals by making them immune to the disease, and it protects whole populations by hindering the spread of the infectious agent. Historically, vaccines have consisted of formulations using live, noninfectious (attenuated) microbes that resemble the original pathogen whole organisms that have been killed or purified by-products of the infectious agent. More recently, some vaccines have...

Plant Vaccines

Transgenic Plant Production of Vaccine- and Antibody-Like Biopharmaceuticals against Some Important Human Diseases Vaccine Antibody Thus, each participant received potato cubes from a random sample of non-transgenic control or transgenic tubers. Prior to and at multiple time points after ingestion of the potato, serum and fecal samples were taken and analyzed. A significant rise in LT-B antibodies was displayed by 10 of the 11 test participants, whereas no LT-B-specific antibodies were detected in control volunteers. Interestingly, serum antibody levels induced by ingestion of the transgenic potatoes were comparable to those measured when participants were challenged with 106 virulent enterotoxigenic E. coli organisms (Tacket et al., 1998). Also, other human trials are currently in progress using orally-delivered, potato-derived HBsAg as booster for the commercial hepatitis B vaccine and potato-delivered Norwalk virus virus-like particles for a viral diarrhea vaccine (Thanavala et...

Medical indications of the acquired immune response

Acquired immune response is vaccination. The simple and elegant theory of vaccination is that induction of a primary immune response by a nonpathogenic form of an antigen leads to immunity of the infectious form. Common types of vaccines are attenuated pathogen, related noninfectious antigen, and purified proteins from the pathogen. Examples of all of these vaccines have been used to induce a primary immune response that confers acquired immunity. See also Affinity maturation Antigen-presenting cells Antigens, T dependent and independent Immune response Immunoglobulin class switching Maternal antibodies Memory, immunological Vaccines.

Characteristics of the organism and its antigens

The Ads of different serotypes have an icosahedral architecture, a double-stranded linear DNA, and more than 12 structural proteins, three of which are major components of the capsid (Figure 1). There is no virus envelope 240 hexons, each a trimer of identical polypeptides, are the major subunits of the 252 capsomere shell with 12 different structures called pentons at each of the vertices. The penton is composed of five penton base and three fiber polypeptides which project out from the base in an antenna-like structure. These polypeptides are antigens for host immunologic responses to natural and vaccine-associated infection. The internal structural proteins are divided into those associated with the DNA in a core-like structure and others that bind to the inner surfaces of the hexon or penton capsom-eres. None of the internal proteins appear to be involved in humoral or cell-mediated immunity.

Hydrophobic compounds and surfactants

The use of emulsions began in the 1930s with the experiments of Freund, who mixed paraffin oil with solutions of killed mycobacteria. This compound, called Freund's complete adjuvant, is one of the most potent adjuvants known. It is, however, too toxic for use in humans. An oil emulsion without the mycobacteria, called Freund's incomplete adjuvant, is less toxic and was clinically utilized in the past for influenza and poliomyelitis vaccines. It is no longer used because of a low incidence of induced sterile abscesses, the question of carcinogenicity in mice, lot-to-lot variation, lack of long-term stability, and the fact that CMI is not substantially boosted. Saponin is a compound that was initially purified from the bark of the tree, Quillaja saponaria. It has been studied for decades, but is too toxic for use in humans. Chemical extraction procedures led to the less toxic derivative, Quil A, which is utilized widely for veterinary vaccines, and subsequently to QS21. Complexes of...

Living organisms as vectoradjuvants

An exciting recent approach is to engineer genetically a nonpathogenic but infectious living organism to deliver foreign protective antigen(s) to the immune system. The vaccine recipient is infected with the organism, which is utilized as a vector in order to induce an immune response to the antigen. The first live vector to be utilized was vaccinia virus however, many other viral or bacterial vectors are now being developed to deliver protective antigens to the immune system. One excellent candidate for the construction of such an attenuated vaccine is BCG, which has already been extensively utilized worldwide in humans as a vaccine that has a very low incidence of serious side-effects. Attenuated Salmonella or Shigella strains that stimulate local immune responses after oral immunization are also being developed. Viruses, including adenovirus or polio-virus, have considerable potential for the ability to deliver foreign antigens to the immune system. Recombinant poxvirus vectors...

Welfare Problems Of Industrialized Agrictulture

For these reasons, the values of industry business efficiency and productivity supplanted the values and way of life of husbandry. One casualty was animal welfare, as technological sanders such as antibiotics, vaccines, air-handling systems, and hormones allowed us to force, as it were, round pegs into square holes. Productivity was severed from well-being, with animals now suffering in ways that were irrelevant to productivity and profit. Industrialized confinement agriculture in fact brought with it at least four major new sources of suffering and welfare problems

Diseases And Their Control

Aquatic animals are susceptible to a variety of diseases, including those caused by viruses, bacteria, fungi, and parasites. A range of chemicals and vaccines has been developed for treating the known diseases, although some conditions have resisted all control attempts to date, and severe restrictions on the use of therapeutants in some nations has impaired the ability of aquaculturists to control disease outbreaks. The United States is a good example of a nation in which the variety of treatment chemicals is limited (Table 6). In many instances when a drug is cleared for use on aquatic animals in the United States, the species on which the drug can be used is limited. Clearing a drug for catfish, for example, does not necessarily mean it can be used on trout. The cost of obtaining clearance for drug and chemical use can be in the millions of dollars, and it is often uneconomical to attempt gaining clearance for species that are not major contributors to overall aquaculture...

Evidencebased infectious diseases

Pasteur, on developing an animal vaccine for anthrax, vaccinated a number of animals with members of the media in attendance.4 When unvaccinated animals subsequently died, while vaccinated animals did not, the results were immediately reported throughout Europe's newspapers. Having led the developments in both classical and clinical epidemiology, is current infectious diseases practice evidence-based We believe the answer is somewhat . We have excellent evidence for the efficacy and side effects of many modern vaccines, while the acceptance of before-after data to prove the efficacy of antibiotics for treating bacterial meningitis is ethically appropriate. In the field of HIV medicine we have very strong data to support our methods of diagnosis, assessing prognosis and treatment, as well as very persuasive evidence supporting causation. However, in treating many common infectious syndromes -from sinusitis and cellulitis to pneumonia - we have many very basic...

Preclinical Testing For An Established Excipient

Cross-reference to published scientific reviews of the safety of materials used as excipients in a drug formulation is acceptable to the regulators. More and more reviews are becoming available for materials used as excipients. Examples of recently reviewed materials are the CDs (36,46,47), the HFAs (73), lactose (82), methyl and propyl paraben (83,84), peppermint oil, and menthol (52) PEG (85) polysorbates (Tweens) (86) and polyvinylacetate phthalate (42), polyvinylpyrrolidone (PVP) (87), propylene glycol (88), sodium metabisulfite (89), and trehalose (90). Even a new vaccine adjuvant monophosphoryl lipid A, which in terms of a constituent of a drug formulation can be considered an excipient, has been recently reviewed (40). The cross-reference process needs to involve a robust scientific appraisal of the published data, with comment on the relevance of any animal findings to humans in the new proposed formulation, together with the establishment of safety margins. Animal toxicity...

Prevention and Treatment

Both normal and distorted prion proteins fail to stimulate any detectable host immune response, and no inflammatory reaction is associated with accumulations of abnormal prion protein in neurons. The agent presents special challenges to those attempting to develop effective drugs for treatment and vaccines for prevention.

Antigenic variation and immunity

Antigenic variation of protozoans, bacteria and animal viruses provides a mechanism for persistence of the organism in its host, but makes immunological control difficult. The strategy used for the development of influenza A virus vaccines has been to identify the circulating strains early in the influenza season and to rapidly produce a vaccine against the predominant strains. In lentiviruses this strategy cannot be used because mutation and selection occur in a single infected host. Thus a wide repertoire of neutralizing epitopes must be included in a vaccine to prevent the evolution of lentiviruses that can evade the host immune response. See also Influenza virus (orthomyxovirus), infection and immunity Parasites, immunity to Rhabdovirus, infection and immunity Trypanosomiasis, African Vaccines Viruses, immunity to.

Type 2 Tindependent antigens

(GM-CSF) synergistically induce the IgG3 switch in murine B cells exposed to polysaccharides. Conjugate vaccines of polysaccharides linked to proteins induce cognate T-B interaction. Their utilization to enhance defense against encapsulated bacteria in infants and splenectomized or otherwise immunocompromised adults is of medical importance.

Molecular Characterization Of B Pertussis And B Parapertussis

Molecular characterization and typing of B. pertussis and B. parapertussis are used to obtain information on the changes in the phenotype and genotype of circulating isolates and in epidemiological studies. When polymorphisms in a number of B. pertussis genes encoding for virulence factors and surface-associated proteins as well as in housekeeping genes were studied, B. pertussis proved to be a rather conserved bacterium. Polymorphisms in recent isolates are restricted to genes encoding tracheal colonization factor, pertactin (Prn), and the S1 subunit (ptxSl) of PT. 9,14 Pertussis toxin and pertactin are important virulence factors and protective antigens. Pertussis toxin is a component of all and Prn of many new acellular vaccines and, thus, the degree of allelic variation in genes encoding these proteins has been studied intensively in many countries. The majority of the currently circulating isolates express PT and Prn types that are different from types included in the vaccines...

Molecular Testing In The Epidemiological Typing Of B Pertussis Isolates

The finding that the currently circulating strains harbor ptxS1 and prn alleles different from those in strains used for vaccine production emphasizes the importance of monitoring the molecular evolution and antigenic variation of clinical isolates. In epidemiological studies, PFGE is used for the determination of the overall genotype of the isolates. Serotyping and the determination of ptxS1 and prn alleles provide information about the expression and polymorphism of these virulence factors at a singlegene level. To date, the only way to determine alleles encoding for important antigens has been PCR-based sequencing, a relatively time-consuming and expensive method. Thus, new simple methods suitable for large-scale screening of isolates are needed. Recently, real-time PCR using fluorescent-labeled hybridization probes has been applied to the determination of prn and ptxS1 alleles of B. pertussis 24,25 These assays proved a good alternative to sequencing as they correctly identified...

Bare lymphocyte syndrome Type I

Clinical investigations of these type I BLS patients are remarkable in that susceptibility to pulmonary bacterial infections predominate. Peripheral blood CD8+ T lymphocyte levels are low and there appears to be no or very low natural killer cell function in these individuals. In contrast, high antibody titers against bacteria and viruses, as well as good responses to vaccination are found in these BLS type I patients. The enhanced frequency of respiratory tract bacterial infections in these patients suggests class I antigens on phagocytic cells such as macrophages must play a key role in immunity against these pathogens.

Recommendations administration and efficacy

The inconsistent policies among countries with regard to the indication for administering BCG vaccine reflect the contradicting and inconclusive data on the prevention of TB and the drawback of a resultant tuberculin seroconversion preventing the interpretation of the tuberculin skin test. BCG is presently recommended in the USA for tuberculin-negative infants and children who have continuous exposure to isoniazide- and rifampin-resistant active TB, who cannot take isoniazid and are exposed to TB, or who belong to population groups with rates of new M. tuberculosis infections exceeding 1 per year. Vaccination is also advised for groups residing in high-prevalence areas such as military and foreign service personnel. Vaccination should be avoided in immunosuppressed individuals, with special regard to patients with established human immunodeficiency virus (HIV) infection because of the increased risk of disseminated infection.

The Significance Of Infectious Agents In The Causation Of Neoplasia

As noted in Chapter 1, the possibility that infectious agents are a significant cause of neoplasia was quite popular in the latter part of the nineteenth century. However, the popularity of this concept decreased during the twentieth century until about four decades ago, when several of the oncogenic viruses became known and subsequently were characterized both biologically and in a molecular sense. It is difficult to ascertain the importance of infectious agents as causes of neoplasia in lower forms of animals in their natural habitat, but it is apparent, as can be seen from many of the discussions in this chapter, that infectious agents can be a significant causative factor for neoplasia, either induced or spontaneous, in domestic and laboratory animals. As discussed in Chapter 12, infectious agents as causative of human cancer may represent as much as 15 of the total cancer problem. While this may seem alarming, it also presents the possibility that various preventive measures such...

Indicators of central tendency mean median and mode

2.2.1 Mean - 10 batches of vaccine Our first example set of data concerns a series of batches of vaccine. Each batch is intended to be of equal potency, but some manufacturing variability is unavoidable. A series of 10 batches has been analysed and the results are shown in Table 2.1. Table 2.1 Potency of 10 batches of vaccine (units ml) Figure 2.1 The mean satisfactorily indicates a typical potency among 10 batches of vaccine

Immune response of the host

Humoral and cell-mediated immune (CMI) responses to pertussis are poorly understood. Neutralizing antibodies are considered to be a major protective mechanism against infection with B. pertussis. Recent vaccine trials demonstrated that antibody levels to B. pertussis antigens including PT, FHA, PRN and fimbriae correlate with protection against pertussis. In addition, a nonlethal pertussis infection provides long-term immunity to subsequent pertussis, and recovered patients produce anti-B. pertussis immunoglobulin A (IgA) in serum and saliva, suggesting the importance of mucosal antibodies. lowing vaccination or infection. In mice, high anti-B. pertussis IgG correlates with rapid clearance of the bacteria in a respiratory infection model but a pertussis-specific CMI response is required for complete elimination of the organisms from lungs. B. pertussis survives in human monocytes and other mammalian cells in vitro, and a CMI reponse may be necessary for eliminating this potential...

Mammalian Cell Cultivation

Bioreactors developed for mammalian cell culture use a smooth surfaced ceramic for the growth of adherent cells or a porous ceramic for the immobilization of suspension cells. Mammalian cell culture technology has been used for the production of viral vaccines, monoclonal antibodies for diagnostic and therapeutic use, interferons, interleukins, growth factors, and blood regulation proteins. The design of novel bioreactors for mammalian cell culture must take into consideration process constraints such as cell line distribution, product formation, oxygen transfer, nutrient supply, and shear. A viable alternative to scalable mass cell culture is the use of bioreactors with ceramic matrices. Immobilization of adherent and suspension cells on these surfaces has resulted in the favorable production of both cells and cell derived proteins. Cell culture densities ranging For the cultivation of anchorage dependent animal cells, packed bed bioreactors have been used. Such reactors up to 100 L...

Evasive strategies of the virus

The FCV capsid protein is known to be variable (above). FCV comprises a single serotype but variation is such that sequential infection by antigenic variants is possible. During infection (persistent or acute), the antigenic profile of the virus may drift virus isolated later in infection may be more vaccine resistant. This drift may allow the virus to resist herd immunity. It may also affect pathology by influencing host tissue range for example, enteric forms of FCV resist bile salts, while respiratory forms do not. However, bile-resistant variants can be selected from bile-sensitive populations. Monoclonal antibodies may differentiate between strains associated with different clinical presentations, implying that some determinants of pathology may be close to antigenic regions.

Immune response to carbohydrates

The early discovery that the 'soluble-specific substance', the capsular material of Streptococcus pneumoniaer, is immunogenic in humans prompted immunizations with purified polysaccharide in the early 1940s. The contemporary and subsequent great success of the treatment of pneumonia with antibiotics rapidly diminished the initial interest in vaccines. However, the continued frequency of serious diseases such as pneumococcal meningitis, and the appearance of bacterial strains showing resistance to antibiotics, including S. pneumoniae, has rekindled an intense interest in immunization with polysacchar-ide-based vaccines. Unfortunately, polysaccharides themselves are often poor immunogens, particularly in infants and in immunocompromised individuals. In addition, for pneumococci, the existence of 84 distinct serotypes has complicated the issue. For this organism, penicillin resistance is concentrated amongst the (pediatric) serotypes 6, 14, 15, 19 and 23, while types 1, 2, 3 and 4 are...

Haemophilus Immunization

H influenzae type b Vaccination in Children Immunized Beginni 2 to 6 Months of Age Vaccine Product H influenzae type b Vaccination When the Initial Vaccination w Delayed Until 7 Months of Age or Older Vaccine Product any vaccine (PedvaxHIB or HibTITER or ActHIB or OmniHIB) any vaccine any vaccine Any vaccine

Indications for Varicella Immunization

Age 12 to 18 months One dose of varicella vaccine is recommended for universal immunization for all healthy children who lack a reliable history of varicella. B. Age 19 months to the 13th birthday Vaccination of susceptible children is recommended and may be given any time during childhood but before the 13th birthday because of the potential increased severity of natural varicella after this age. Susceptible is defined by either lack of proof of either varicella vaccination or a reliable history of varicella. One dose is recommended. C. Healthy adolescents and young adults Healthy adolescents past their 13th birthday who have not been immunized previously and have no history of varicella infection should be immunized against varicella by administration of two doses of vaccine 4 to 8 weeks apart. Longer intervals between doses do not necessitate a third dose, but may leave the individual unprotected during the intervening months.

Revolution in Biology

Following 1953, when Thomas Watson and Francis Crick published their famous paper on the double helix structure of DNA, a series of independent discoveries were made in chemistry, biochemistry, genetics, and microbiology, which together brought about a revolution in biology and led to the first experiments in genetic engineering in 1973. Because of this revolution, scientists learned to modify living microorganisms in a permanent, predictable way. Bacteria have been made to produce medical products, such as hormones, vaccines, and blood factors, that were formerly not available or available only

Pulletgrowing Program

Vaccinations given during the pullet program are the backbone of the layer health program. These programs should contain vaccines against diseases that the pullets will be exposed to during lay. 3 Consideration needs to be given to past disease exposure in the pullet-growing house, diseases present in the region to which the pullets will be moved, and whether the pullets are being moved to a multi-age complex that has a higher degree of disease exposure (such as to Mycoplasma gallisepticum (Mg), Salmonella enteritidis (Se), variant infectious bronchitis (IB) strains, etc.). Professional advice from a competent poultry veterinarian with knowledge of the disease exposure situation, vaccines available, proper timing of vaccinations, and appropriate routes of administration should be sought. An example of a vaccination program used for pullets going to a complex with high risk of exposure to infectious laryngotracheitis (ILT), Mg, Se, fowl pox, and variant IB is given in Table 1. Vaccine...

Biosecurity And Sanitation

Biosecurity programs that prevent the introduction of avian pathogens are an all-important aspect of layer health management, but one that is often not routinely reviewed or given its proper share of capital input. High-risk activities that require attention to details of equipment sanitation, providing people with clean clothing and footwear, and or setting up physical decontamination areas. These activities include bird moving (point-of-lay pullets, spent fowl, fill-in birds), egg handling materials (pallets, reused egg flats), vaccination crews, beak-trimming crews, welfare auditing, veterinary visits, flock supervisor visits, repair person visits, and so forth.

Preventive Medications

Even though the use of cage growing has greatly minimized the use of coccidiostats and antibiotics, some cage units that have had coccidiosis in the past also use coccidiostats for selected times during growing. Although vaccination is the most common method of preventing Mg, some producers use government-approved antibiotics for all or part of the lay cycle in order to prevent this disease (Table 2).

General References

In this type of specific immunity, the antigen causes certain groups of primed white blood cells to act specifically against the invading antigen. These WBCs can ingest or destroy the antigen as well as proliferate chemical messengers signaling the presence of non-self material. It seems that immersion-vaccination results in eliciting a particularly strong cellular immunity. This type of immunity is also referred to as cell mediated immunity. The following are various cell types involved in cell mediated immunity.

Use Of Blood Plasma In Foods

Purified bovine albumin is used in testing for the Rh blood factor in humans, as a stabilizer for vaccines, and in antibiotic sensitivity tests. Cattle blood is also a good source of superoxide dismutase, which is used to treat ischemia, osteorarthritis, and other types of inflamma-

Traditional Veterinary Health Programs

Traditional health care programs are based on the veterinarian providing services to diagnose and treat diseases, recommend vaccination and anthelmintic programs, perform basic surgeries, test for reportable diseases, and perform rectal palpation for pregnancy diagnosis and breeding examination of cows. 2-4 These services are not much different from those described by Hawarth in 1673. Only technical expertise and knowledge are greater. Veterinarians report that the most frequent activities in cattle practice are physical exam, disease diagnosis and treatment, castration and dehorning, and advice on vaccination and anthelmintic programs (Table 1). 3,4 Producers request service as they see problems in the herd. Traditional veterinary programs are based on the epidemic concept of disease. 5 Disease is caused by a specific agent (bacteria, virus, or other infectious agent) or a specific factor (deficiency, toxicity, irritant, genetic defect). 2 Treatment is specific for the agent, and...

Special Medications

-Immunoglobulin (IVIG) 2 gm kg dose IV x 1 dose. Administer dose at 0.02 mL kg min over 30 min if no adverse reaction, increase to 0.04 mL kg min over 30 min if no adverse reaction, increase to 0.08 mL kg min for remainder of infusion. Defer measles vaccination for 11 months after receiving high dose IVIG. inj 50 mg mL, 100 mg mL

Experimental Autoimmune Encephalomyelitis

It was reported that a small percentage of patients receiving Pasteur's rabies vaccine developed neuroparalytic signs. The rabies virus vaccine was prepared in rabbit CNS tissue. That CNS antigens contaminating the vaccine preparations were probably responsible for the neurological side-effects of the vaccine was demonstrated in the 1930s, by Rivers and his colleagues, who reported that repeated intramuscular injection of extracts of normal rabbit brain (i.e. without rabies virus) induced pathologic changes in the brains of monkeys these changes resembled the CNS disease that occurred in humans subsequent to rabies vaccine treatment. With the development of Freund's adjuvant in the 1940s, it became possible to reproducibly elicit EAE in a majority of animals after a single injection of CNS extract emulsified in the adjuvant preparation.

Basic and Applied Research

In addition to carrying out basic research, molecular biologists may also work in applied research. Using recombinant DNA technology, for example, molecular biologists have created economical vaccines against deadly diseases. The molecular biologist often works at the frontier or cutting edge of a discipline. The rewards of such work include the thrill of intellectual discovery and the opportunity to conduct independent research. Also, the efforts of molecular biologists can bring great benefits to society.

Late Infancy 6 to 18 Months

PHYSICAL ASPECTS Normal infants triple their birth weight by 1 year of age, but the rate of growth slows during this period. The primary teeth begin to erupt by 6 months of age, with an average rate of acquisition of one per month. Head size, center of gravity, and surface area to mass ratio remain large in comparison to adults. The anterior fontanelle is closed by 18 months of age. The measles-mumps-rubella (MMR) vaccination is given at 12 to 15 months of age, and the varicella vaccine is given at 12 to 18 months of age. The DPT and HIb boosters are given during this same period (Iable,111-3).

Evasive strategies by the organism

Induced lysis and gives resistance to intracellular killing by polymorphonuclear leukocytes. This resistance is a virulence trait, which is lost in the attenuated live vaccine strain F. tularensis LVS. LVS is efficiently killed by polymorphonuclear leukocytes due to strictly oxygen-dependent mechanisms. Both a wild strain of F. tularensis and LVS induce a respiratory burst in the phagocytes during endocytosis, but only LVS is susceptible to the hypochloric acid and hydrogen peroxide produced as a result of the burst. The actual virulence factor has not been identified.

Changes in the food production chain and food industry structure

Not all changes in the food production and marketing chain have resulted from technological advances - some changes are due to other factors such as a balancing of global supply and demand for certain food products. Additionally, some changes in the food production chain may increase some food safety risks or alter the mix of risks. For example, the use of aquaculture is becoming more common as wild fisheries become increasingly over-harvested and less cost-effective for some species and areas. US aquaculture production increased by over 50 between 1990 and 2000 (NMFS, 2002) and the aquaculture share of the world production also has increased (FAO, 2000). Farm-raised fish pose a different set of food safety challenges from those of wild-caught fishery products. Farm-raised fish are subject to contamination from residues by production inputs (e.g. vaccines, feed additives, and antibiotics), whereas wild-caught seafood may be more subject to histamine risks from poor temperature control.

Immune deficiencies or immune disorders and gene therapy

With natural sites present on the provirus, regulated production of IFN a and IFN (i able to interact with viral production, intracellular synthesis of neutralizing antibodies against viral proteins, and expression of ribozymes able to specifically cleave R MA viral genomes. In addition, gene therapy vaccine approaches are now under development. Fven if T lymphocytes were first proposed as target cells, it appears that difficulties in genetically modifying this ccll population ex vivo when derived from HIV-positive patients dictated the consideration of hematopoietic progenitors as target cells and retroviral vectors as gene transfer tools to promote therapeutic-activity in cell lineages involved in HIV infection. This approach would have the significant advantage of allowing therapeutic information to persist during the lifespan of the patient and of expressing the transgene of interest in dendritic cells and macrophages as well as in CD4' T lymphocytes Table 2).

Chapter References

Adams WG, Deaver KA, Plikaytis BD, et al Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA 269 221, 1993. 14. Black S, Schinefield H, Ray P, et al Efficacy of heplavalent conjugate pneumococcal vaccine (Wyeth-Lederle) in 37,000 infants and children Results of the Northern California Raiser Permanente Efficacy Trial. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, Sand Diego, Sept. 24-27, 1998 (abstract).

Helicobacter pylori infection

The development of effective vaccine is also an interesting area in the prevention of H. pylori infection. However, the ability of recombinant Lactobacillus or other probiotics to be used as an antigen-delivery vehicle to induce protective immune response have rarely been studied. In the first study by Lee et al. (2001), Lactococcus lactis producing cytoplasmic Urease B was shown to be unable to induce protection against H. pylori in a mouse model. In contrary, recombinant L. plantarum strain producing H. pylori Urease B subunit was found to induce successfully a partial mucosal protection against Helicobacter (Corthesy et al., 2005).

Genetic variation of HBsAg

This particular mutation has been found in a number of vaccine recipients around the world and in one patient not known to have been immunized. This virus was also shown to be transmissible in chimpanzees, and in mice the variant HBsAg, although eliciting a high titer antibody to the variant, produced only a low titer of antibody recognizing the native protein. Other variants of HBV which have amino acid changes in the common 'a' determinant have now been described in patients and vaccinees with chronic liver disease. The effect of these mutations on the

Rheumatic valve disease

Ter of time before it becomes resistant (resistance to erythromycin, the second drug of choice, is common and seems to be increasing). Recently, important progress towards the development of an effective vaccine to protect against streptococcal nasopharyngeal infection opens up the possibility of better control of rheumatic fever.5

First Applications Of

The potential for improvement in the area of pharmaceutical contamination control was evident in Cooper, Hochstein, and Seligman's very first application of the LAL test involving a biological (3) the results of 26 influenza virus vaccines included as a subset of a 155 sample test using LAL varied from lot to lot by up to 1000-fold and revealed endotoxin in the 1 mg range in the 1972 study. Cooper and Pearson (4) later pointed out that newer vaccines used in mass inoculation of Americans for A swine virus were subsequently required to contain not more than 6 ng mL of endotoxin, a level that could not be demonstrated with pyrogen testing. Suspected adverse reactions were reported prior to the inception of the LAL assay and were an expected part of some drug reactions such as that associated with L-asparaginase antileukemic treatment as a product of Escherichi coli (5). Another early application on radiopharmaceuticals and biological vaccines mentioned earlier involved the detection of...

The immunology of HIV infection

Antibodies and this factor has driven vaccine development. Because this region is highly variable, the virus is able to escape a strong antibody response. Moreover, it is not clear that disease progression is greatly influenced by neutralizing antibodies on their own as the immune response broadens to different V3 loops as disease progresses. Therefore, the nature of the protective immune response that clearly exists in long-term partners of AIDS patients must be defined in detail and the mechanism of how the virus induces disease needs to be carefully elucidated. Unfortunately, after over a decade of research the answers to these questions are only just beginning to be more than just theoretical.

The immune response to HIV and the correlates of protection

HIV induces neutralizing antibodies, antibody-dependent cellular cytotoxicity (ADCC), and cytotoxic T lymphocyte (CTL) activity in infected hosts. Unfortunately, it remains unclear as to whether any one, or all, of these activities can prevent infection and disease progression in the majority of individuals. It is important to appreciate that the quality of the immune response that protects against infection and the type of response required to contain infection may be different. This, of course, will have important implications for the development of preventative and therapeutic vaccines. This problem is further compounded by the fact that HIV-infected chimpanzees do not appear to develop an AIDs-like disease, and hence they may have a vital immunological difference that allows a vaccine to prevent HIV infection that will not extrapolate to protection of humans against the same infection.

Manipulated responses Passive immunization

The immune system can be directly stimulated by injection of an antigen into the organism. Such an active immunization is referred to as vaccination. In a humoral response, B cells will be activated and differentiate into plasma cells and memory cells. Thus long-term protection will be achieved. The enormous power of vaccination can be seen in the fact that by this means diseases such as polio or diphtheria can be controlled or even, in favorable circumstances, eradicated (smallpox). See also Acute inflammatory reaction Affinity Affinity maturation Agglutination Antibody-dependent cellular cytotoxicity Antigen-binding site Autoimmunity Mast cells B lymphocyte differentiation Cell-mediated immunity Helper T lymphocytes Complement receptors Cytokines Diversity, generation of Fc receptors Germinal center Hypersensitivity reactions Immune adherence Immunoglobulin class switching Immunoglobulin, functions Immunoglobulin structure Lymphocytes Memory, immunological Neutralization of...

Pressureaugmented immunogenicity

Pressurized tumor cells, as well as pressurized autoimmune cells, were both demonstrated to possess a high and specific immunogenicity. Such pressure-treated cells were successfully used in pre-vaccination trials in murine models of cancer and autoimmune diseases. These observations open novel approaches for both the diagnosis and treatment of cancer and autoimmune disease, which are currently under investigation. See also Antigen presentation via MHC class I molecules Antigen presentation via MHC class II molecules Gravity, effect of space flight on immunity Membrane-associated cytoskeleton role in regulating immune cell function Stress proteins T cell vaccination.

Preexposure Prophylaxis

Preexposure prophylaxis with rabies vaccine is highly recommended for persons whose recreational or occupational activities place them at risk for acquiring rabies veterinarians and staff, animal-control and wildlife workers, travelers visiting foreign areas of enzootic rabies for more than 30 days, and veterinary students. Although the initial rabies preexposure vaccine regimen is similar, the need for booster doses, the timing of booster doses, and the need and timing of serologic tests to confirm immunity differ based on the degree of individual risk for exposure to rabies.19 Emergency medicine health care providers should refer persons at risk for rabies who have not received preexposure prophylaxis to their local physician or health department for appropriate immunization. Preexposure vaccination does not eliminate the need for additional therapy after a rabies exposure, but simplifies postexposure prophylaxis by eliminating the need for human rabies immune globulin (HRIG) and by...

Prior Rabies Immunization

If exposed to rabies, persons previously vaccinated should receive two intramuscular doses (1 mL each) of vaccine, one immediately and one three days later. 19 Previously vaccinated refers to persons who have received one of the recommended preexposure or postexposure prophylaxis regimens of HDCV, RVA, or PCEC, or those who have received another vaccine and had a documented rabies antibody titer. HRIG is unnecessary and should not be given in these cases because an Immunization of immunocompromised persons presents special challenges. First, vaccines may represent a danger to the immunocompromised person. Second, the immune response of immunocompromised persons to vaccination may not be as good as that of immunocompetent persons higher doses or additional immunizations may be required, although even with these modifications, the immune response may be suboptimal. The Advisory Committee on Immunization Practices (ACIP) considers these persons severely immunocompromised congenital...

Human Immunodeficiency Virus

HIV is an enveloped genome of two identical, single-stranded RNA molecules. HIV, classified as a retrovirus in the subfamily lentivirus, replicates in activated CD4 T lymphocytes. There are two types of human lentiviruses HIV-1, the predominant HIV type in most parts of the world, and HIV-2, primarily found in West Africa. 58 As of December 1996, the Joint United Nations Programme on HIV AIDS estimated that there were a total of 27 million adults and 2.6 million children with HIV infection. Of these cases, 62 percent occurred in sub-Saharan Africa and 23 percent in South and Southeast Asia. 59 As of 1996, there were at least five African nations with adult prevalence of HIV greater than 10 percent. In 1996, there were over 32,000 deaths in the United States due to HIV and or AIDS, ranking it the eighth leading cause of death in the nation.60 The capacity of HIV to recombine and generate mosaic genotypes confounds treatment efforts and vaccine development. The virus mutates at varying...

Antigenspecific methods

Use of ultrapure (recombinant) allergens in classical immunotherapy protocols offers homogeneity, reproducibility and perhaps improved efficacy compared to the complex mixtures that currently dominate clinical practice. Several approaches (i.e. chemical modification of allergens, DNA vaccines) have been proposed that aim to reorient ongoing cytokine response in vivo from those of TH2-associated bias to TH1-dominated patterns. Alternatively, by identifying the immunodominant peptides driving allergen-specific T cell reactivity in humans, it may be possible to functionally delete them from the periphery upon inhalation, injection or oral administration. Each of these strategies focuses on altering the activity of allergen-specific regulatory populations (largely but not exclusively CD4 T cells) responsible for maintaining the allergic state.

Lamivudineassociated Mutations In The Hbv S Gene

Four open reading frames, the S, C, X, and P genes, have been identified within the HBV genome. Because of the overlap of the P and S genes, lamivudine-associated mutations produce changes in the S gene, too. Consequently, lamivudine-resistant HBV isolates show alterations in the ''a'' determinant of the HBsAg protein. 16 Lamivudine-selected HBsAg protein changes may have important virological and clinical implications They may escape neutralization by vaccine-induced anti-HBs antibodies and thus may have the potential to become vaccine escape mutants. Widespread use of lamivudine may lead to infection of vaccinated individuals and potentially reduce the efficacy of current HBV vaccines.

Infection and humoral immunity

Mucosal (IgA) and serum (IgG) antibodies to the HA molecule neutralize virus infectivity and are primarily responsible for resistance to reinfection. This is the basis of vaccination against current epidemic strains with killed virus. The immunoglobulin (Ig) response to the HA is subtype specific, but accumulation of point mutations (antigenic drift) permits infectious virus to escape antibody-mediated destruction. Five antigenic sites, all of which are associated with protection, have been identified on the globular head of the HA molecule. 'Antigenic drift' results from the accumulation of amino acid substitutions at these sites, reproduced in the laboratory by selection of escape mutants with mouse monoclonal antibodies (mAbs). In addition, crystal-lographic studies with the mutants have shown that the antibodies bind to the regions of the molecule where the amino acid substitutions occur.

Shaken Optimism about Modern Medicine

Parsons believed, along with many scientists in the 1960s and 1970s, that modern medicine verged on conquering all major infectious diseases, at least for societies with effective systems of sanitation and public health. The appearance in the 1980s of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) has shaken such optimism. It has now become clear that humankind faces a major pandemic that, despite modern science and technology, will take scores of millions of lives globally (WHO). Twenty years of research has failed to produce an effective vaccine. New antiretroviral medications are extending the life and health of many patients with HIV AIDS, but not all patients are helped, and how long the others will benefit remains unclear (IAPAC). In the meantime, many patients do not receive the new treatments because they have not been diagnosed, are not willing to face the consequences of an HIV AIDS diagnosis, lack access to care or means of paying for...

T cell specificity and memory

Influenza-immune CD4+ helper T cells are specific for viral peptides presented in the context of self MHC class II glycoproteins. Following infection, the normal sequence of events is that antigenic determinants on the viral coat glycoproteins are bound by lg receptors on appropriate B lymphocytes. This leads to the interiorization of the virus-Ig complex, degradation in lysosomes, and expression of constituent peptides + MHC class II molecules on the surface of the B cell. Lymphokines, such as IL-2 and IL-4, that are needed to promote the growth and differentiation of B lymphocytes specific for the influenza hemagglutinin (HA) molecule, can thus be provided by T helper cells reactive to epitopes derived from any of the viral proteins. This may be one reason why whole, inactivated influenza virus vaccines are more effective than, for instance, those consisting solely of HA subunits. via MHC class I molecules Antigen presentation via MHC class II molecules Antigenic variation B...

The Importance of SNPs

mutation suggests a nucleotide change that prevents a protein from performing its normal function. These mutation-caused changes are rare, occurring in less than 1 percent of the population. This type of genetic mutation is almost always severe enough that its presence alone is enough to cause the disease. In contrast, SNPs are much more common, certainly occurring in more than 1 percent of the population. Their presence may make it easier for a person to get a specific disease, but they do not cause the disease by themselves. Instead, disease can occur only in the presence of the correct environment, other gene combinations, drugs, and other such factors. This is very important, for it suggests that by knowing that an individual is at risk for a disease, a doctor can take actions to prevent it. These actions may be as simple as a dietary or lifestyle change, or taking a medicine or vaccine.

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