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

Abstract

The immunogenicity of a type 2 herpes simplex virus (HSV-2) antigen preparation following its formulation into immunostimulating complexes (ISCOMs) or non-ionic surfactant vesicles (NISV) was investigated in a murine model. The immune responses induced by each formulation were characterised by antigen specific total and subclass serum responses, and by lymphocyte proliferation and cytokine (interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma)) production by in vitro restimulated spleen cells. The degree of protection afforded to mice by these various HSV-2 vaccine preparations against homologous (HSV-2) and heterologous (HSV-1) challenge infection was also determined. The findings suggest that formulation of the HSV-2 glycoprotein antigens with ISCOM or NISV delivery vehicles, and the methods 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 immunised with the HSV-2 ISCOM formulated vaccine preparation. Furthermore, although HSV-2 antigens formulated in dehydration-rehydration NISV, or entrapped 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 lymphoproliferative responses, formulation of HSV-2 antigens by freeze-thawing with NISV at 60 degrees C (HSV-2 NISV 60) did not. There were no differences between any of the HSV-2 vaccine formulations in terms of IL-4 induction in in vitro stimulated spleen cell cultures. Almost complete protection against HSV-2 challenge was afforded by the HSV-2 ISCOM preparation, while partial protection against challenge infection was afforded by the HSV-2 NISV 30 vaccine formulation. The findings are discussed in relation to the nature of the immune mechanisms, particularly Th1- or Th2-like responses, that may be elicited by HSV-2 antigen preparations formulated into various delivery systems and the relevance of these immune responses to protection against HSV infection in the murine model.

• Authors: S A Mohamedi, J M Brewer, J Alexander, A W Heath, R Jennings
• Journal: Vaccine (Vaccine) Vol. 18 Issue 20 Pg. 2083-94 (Apr 14 2000) ISSN: 0264-410X [Print] Netherlands
• PMID: 10715522 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Antigens, Viral
• Cytokines
• ISCOMs
• Immunoglobulin G
• Surface-Active Agents
• Viral Vaccines

Topics

• Administration, Oral
• Animals
• Antibodies, Viral (biosynthesis, blood)
• Antigen Presentation
• Antigens, Viral (administration & dosage, immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Chlorocebus aethiops
• Cytokines (blood)
• Female
• Herpes Simplex (prevention & control)
• ISCOMs (administration & dosage, immunology)
• Immunization, Secondary
• Immunoglobulin G (biosynthesis, immunology)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Simplexvirus (growth & development, immunology)
• Spleen (immunology)
• Surface-Active Agents
• Vaccination
• Vero Cells
• Viral Vaccines (administration & dosage, immunology)
• Virus Cultivation