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IgG subclasses differ in their effector functions in a variety of in vitro assays. To assess the effect of antibody subclass differences on in vivo protective efficacy against herpes simplex virus (HSV), a series of subclass switch mutants was made from an anti-HSV glycoprotein D monoclonal antibody. Purified antibody was examined for the ability to protect against HSV-2 challenge in mice. IgG2a was found to be more effective than IgG1. This correlated both with activity in antibody-dependent cell-mediated cytotoxicity and with efficiency of complement-mediated neutralization. These data suggest that optimization of passive immunization against HSV requires consideration of antibody subclass.

An experimental AIDS vaccine based on attenuated, recombinant vesicular stomatitis virus (rVSV), when administered by a combination of parenteral and mucosal routes, has proven effective at preventing AIDS in a rhesus macaque model (Rose NF, et al.: Cell 2001;106:539-549). In an effort to determine the optimal route of vaccine administration we evaluated the ability of rVSV-based vaccine vectors expressing HIV-1 Env and SIV Gag proteins, when given either intramuscularly (i.m.) or intranasally (i.n.), to elicit antigen-specific cellular and humoral immune responses, and to protect from a subsequent vaginal challenge with simian-human immunodeficiency virus (SHIV89.6P). Our results demonstrate that macaques vaccinated by the i.n. route developed significantly higher antigen-specific cellular immune responses as determined by MHC class I tetramer staining, IFN-gamma ELISPOT, and cytotoxic T cell assays. However, systemic and mucosal humoral immune responses did not vary significantly with the route of vaccine administration. Given the importance of cell-mediated immune responses in slowing AIDS progression, intranasal delivery of a VSV-based AIDS vaccine may be an optimal as well as practical route for vaccination and should be considered in design of clinical trials.