The Characterisation of Antibody Responses to Different Herpesvirus Vaccine Vector Strategies

Abstract

Herpes simplex virus is man's oldest viral enemy. Infections result in symptoms ranging from mild skin lesions to deadly herpes simplex encephalitis, making HSV one of the most costly of viral diseases to treat. Thus the development of a vaccine is imperative. To this end, several vaccine strategies have been utilized to generate immunity to HSV in rodents. These include the use of recombinant DNA, recombinant adenoviruses, and dendritic cells transduced with either of the former and re-introduced to the host to induce immunity. In this study, different aspects of these vaccine types were examined. Antibody and cytotoxic T-cell (CTL) responses to a DNA vaccine encoding gB of HSV-1 (gB-DNA) were evaluated. This resulted in variable long lived antibody responses to a wide range of dosages and CTL responses which followed dose-response relationships. An adenovirus expressing gB of HSV -1 (AdgB) which is able to generate IgA responses (Gallichan et al., 1993) was utilized to determine the best method of mucosal administration to optimize these responses. It was suggested in a previous report that nasal associated lymphoid tissue (NALT) was the desired target for inducing lgA responses (Heritage et al., 1997). Accordingly, the hypothesis was formulated that NALT can produce IgA responses similar to those produced from a combination of inductive sites. To test this hypothesis, mice were immunized either awake or asleep with AdgB assuming that awake delivery restricts induction to the NALT, whereas asleep administration disseminates AdgB throughout the respiratory system. The results demonstrate participation of lower airways in the induction of immunity is desirable for generating IgA responses. Lastly, dendritic cells transduced with AdgB were assessed for their ability to generate systemic and mucosal antibody responses, resulting in the inability to generate IgA, but the ability to generate systemic antibody responses.