A novel generation of viral vaccines based on the ISCOM matrix.
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The effect of subunit vaccination on the incidence and severity of primary and recurrent genital herpes was investigated in the female guinea pig model of herpes simplex virus (HSV) type 2 genital infection. After prophylactic immunization with zwitterionic detergent-solubilized HSV-1 glycoproteins formulated with alhydrogel or as immunostimulating complex particles, significant reductions in the incidence and severity of primary herpetic illness were observed in both vaccinated groups compared with immunization-naive controls. There was a significant reduction in the incidence of spontaneous herpetic recurrences after administration of HSV-1 antigens formulated as immunostimulatory complexes to guinea pigs in a prophylactic mode (P<.01). Increased levels of both postimmunization and postchallenge ELISA and neutralizing antibodies were significant correlates of protection against primary herpetic disease in a prophylactic scenario. However, no correlation was observed between elevated ELISA or neutralizing antibody levels and protection against recurrent disease following prophylactic or therapeutic administration of HSV-1 subunit vaccines.
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Fifteen vaccinated ewes (group 1) and 13 unvaccinated ewes (group 2) were each challenged orally with 2000 sporulated Toxoplasma gondii oocysts at 91 (+/- 1) days' gestation. Another four pregnant ewes acted as unvaccinated unchallenged controls. Lamb mortality in group 1 was 36.4% after a mean gestation of 141 days while in group 2 it was 64.7% after a mean gestation of 131.5 days. These differences were not statistically significant. However, substantially more specific antibody was detected in precolostral sera from live lambs from vaccinated ewes than in live lambs from unvaccinated ewes in group 2.
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To reduce the risks of immunization with killed or live attenuated virus vaccines, it may be advantageous to use a pure, defined antigen that contains determinants for both humoral and cellular immunity. However, although most non-living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL. Indeed, with a few exceptions, it has not so far been possible to induce CD8+ CTL by immunizing with intact soluble proteins. We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL.
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An immunoglobulin G3 monoclonal antibody obtained by immunizing mice with a cell membrane preparation of epimastigotes of Trypanosoma cruzi was shown to agglutinate live epimastigotes, lyse blood-form trypanosomes, and partially protect mice by passive transfer. The main antigens recognized by the monoclonal antibody were located in the flagella of epimastigotes and blood-form trypanosomes. Antigens of epimastigotes, purified by affinity chromatography with the monoclonal antibody, were shown to be highly glycosylated and revealed a wide band with an Mr between 45,000 and 68,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Immunization of mice with a small concentration of the affinity purified antigens incorporated into an antigen delivery system prepared with Quil A (Isotec AB, Lulea, Sweden), a saponin derivative, induced strong antibody and cell-mediated immune responses and protected 100% of the immunized animals against death due to challenge with 100 100% lethal doses of blood form trypanosomes. Protection was due to the use of the antigen delivery system, since mice immunized with equal concentrations of antigens alone or in combination with saponin had 100% mortality. The results suggest that small concentrations of epimastigote antigens obtained by biochemical methods and incorporated into the proper antigen delivery system may serve as a vaccine against Chagas' disease.