title: 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.affiliation: Sheffield Institute for Vaccine Studies, Division of Molecular and Genetic Medicine, Floor 'F', University of Sheffield Medical School, Beech Hill Road, Sheffield, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Mohamedi
authors.forename: J M
authors.initials: JM
authors.lastname: Brewer
authors.forename: J
authors.initials: J
authors.lastname: Alexander
authors.forename: A W
authors.initials: AW
authors.lastname: Heath
authors.forename: R
authors.initials: R
authors.lastname: Jennings
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000097:blood*; D005260:Female; D006561:Herpes Simplex / Q000517:prevention & control; D016882:ISCOMs / Q000008:administration & dosage / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013501:Surface-Active Agents; D014611:Vaccination; D014709:Vero Cells; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014776:Virus Cultivation
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D016882:ISCOMs; D007074:Immunoglobulin G; D013501:Surface-Active Agents; D014765:Viral Vaccines