Antibody responses, cytokine levels and protection of mice immunised with HSV-2 antigens formulated into NISV or ISCOM delivery systems

The immunogenicity of a type 2 herpes simplex virus (HSV-2) antigen prepara tion following its formulation into immunostimulating complexes (ISCOMs) or non-ionic surfactant vesicles (NISV) was investigated in a murine model. T he immune responses induced by each formulation were characterised by antig en specific total and subclass serum responses, and by lymphocyte prolifera tion and cytokine (interleukin-2 (IL-2), interleukin-4 (IL-4) and interfero n-gamma (IFN-gamma)) production by in vitro restimulated spleen cells. The degree of protection afforded to mice by these Various HSV-2 vaccine prepar ations against homologous (HSV-2) and heterologous (HSV-1) challenge infect ion was also determined. The findings suggest that formulation of the HSV-2 glycoprotein antigens with ISCOM or NISV delivery vehicles, and the method s used to prepare these formulations, influenced the immunogenicity of the final preparation. Higher IgG2a and neutralising antibody levels, IL-2 and IFN-gamma levels and lymphoproliferative responses were noted in mice immun ised with the HSV-2 ISCOM formulated vaccine preparation. Furthermore, alth ough HSV-2 antigens formulated in dehydration-rehydration NISV, or entrappe d in NISV by freeze-thawing at 30 degrees C (HSV-2 NISV 30), also elicited relatively high antibody, IL-2 and IFN-gamma levels and relatively high lym phoproliferative responses, formulation of HSV-2 antigens by freeze-thawing with NISV at 60 degrees C (HSV-2 NISV 60) did not. There were no differenc es between any of the HSV-2 vaccine formulations in terms of IL-4 induction in in vitro stimulated spleen cell cultures. Almost complete protection ag ainst HSV-2 challenge was afforded by the HSV-2 ISCOM preparation, while pa rtial protection against challenge infection was afforded by the HSV-2 NISV 30 vaccine formulation. The findings are discussed in relation to the natu re of the immune mechanisms, particularly Th1- or Th2-like responses, that may be elicited by HSV-2 antigen preparations formulated into various deliv ery systems and the relevance of these immune responses to protection again st HSV infection in the murine model. (C) 2000 Elsevier Science Ltd. All ri ghts reserved.