Immune globulin and vaccines

Chickenpox can be prevented by administration of high-titer human varicella-zoster immune globulin (VZIG) by intramuscular injection. In order to be effective, the globulin must be given within 3-4 days after exposure to chickenpox. Based on the schema of pathogenesis (Figure 2), the most likely explanation is that antibody to VZV abrogates the primary viremia and thereby inhibits spread of virus throughout the host.

The medical indications for VZIG include prevention of chickenpox in VZV seronegative children with cancer who are exposed to chickenpox; VZIG is also administered to newborns, especially premature newborns, who are exposed to chickenpox in the postpartum period. Some experts recommend VZIG administration to VZV seronegative pregnant women who are exposed to chickenpox, but there are conflicting data about VZIG efficacy in adults. The data are difficult to interpret because the clinical studies have been performed with two different VZIG preparations (one produced in the USA and another made in Europe). Not only are the VZIG preparations prepared in different facilities, the recommended dosages differ between the European and North American preparations. In the USA, one infant with congenital varicella syndrome has been born to a pregnant woman who received VZIG but still developed gestational chickenpox. These issues have been recently reviewed (see Further reading).

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 from the large clinical trials in the USA, the vaccine is estimated to be 80% effective in children with leukemia. In other clinical trials, the vaccine was administered to healthy children in Japan and the USA. Healthy children require only a single immunization. Immunized children have been followed for several years; over 90% of the vaccinees showed persistence of both cellular and humoral immune responses. Like the children with leukemia, however, a few healthy vaccinees with declining immunity have occasionally contracted breakthrough chickenpox following a community exposure.

Healthy young adults who failed to contract chickenpox as children have been immunized in clinical trials. Two doses of vaccine were required to achieve a seroconversion rate of 92%. Even after two doses, the cellular immune responses of immunized adults were significantly lower than those of immunized children. Furthermore, at 1 year after immunization, the lymphocyte proliferation indices continued to be lower in the adult population.

Finally, varicella immunization has been investi gated in seropositive adults older than 55 years of age, who had a history of wild-type chickenpox as children. Both cellular and humoral immunity was boosted by immunization with live attenuated varicella vaccine. Future studies will investigate whether shingles can be prevented by booster immunization of the elderly.

See also: Attenuated organisms as vaccines; Cytomegalovirus, infection and immunity; Epstein-Barr virus, infection and immunity; Herpes simplex virus, infection and immunity; Herpesvirus-6, infection and immunity; Vaccines; Viruses, immunity to.

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