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Immune response of chimpanzees after immunization with the inactivated whole immunodeficiency virus (HIV-1), three
M Niedrig1, J P Gregersen, P N Fultz
1Department of Microbiology, Behringwerke AG, Marburg, Germany.
Purified whole virus preparations of HIV-1 were produced from supernatants of infected cells and concentrated 5000-fold. After inactivation with formaldehyde, the concentrates were combined with one of three different adjuvants, and used to immunize three groups of three chimpanzees each. The chimpanzees were monitored for HIV-specific humoral and cellular immune responses by ELISA, immunoblot, virus neutralization, delayed-type hypersensitivity, lymphocyte proliferation and antibody-dependent cell-mediated cytotoxicity. Weak and inconsistent responses were observed in animals that received HIV-1 formulated with alum as adjuvant, whereas HIV-1 formulated with incomplete Freund's adjuvant or an experimental adjuvant (BWZL) induced good humoral and cellular immune responses to the virus. The three animals that received HIV-1 with the BWZL adjuvant generated overall the best immune responses; therefore, 2 weeks after the sixth immunization these animals were challenged with infectious HIV-1. Despite the presence of good humoral and cell-mediated immunity, all three immunized animals and a control animal became infected within 4 weeks, as evidenced by repeated isolation of HIV-1 from peripheral blood mononuclear cells and anamnestic antibody responses. The new experimental adjuvant has to be further investigated in other vaccine trials and different animal models.
Purified whole virus preparations of HIV-1 were produced from supernatants of infected cells and concentrated 5000-fold. After inactivation with formaldehyde, the concentrates were combined with one of three different adjuvants, and used to immunize three groups of three chimpanzees each. The chimpanzees were monitored for HIV-specific humoral and cellular immune responses by ELISA, immunoblot, virus neutralization, delayed-type hypersensitivity, lymphocyte proliferation and antibody-dependent cell-mediated cytotoxicity. Weak and inconsistent responses were observed in animals that received HIV-1 formulated with alum as adjuvant, whereas HIV-1 formulated with incomplete Freund's adjuvant or an experimental adjuvant (BWZL) induced good humoral and cellular immune responses to the virus. The three animals that received HIV-1 with the BWZL adjuvant generated overall the best immune responses; therefore, 2 weeks after the sixth immunization these animals were challenged with infectious HIV-1. Despite the presence of good humoral and cell-mediated immunity, all three immunized animals and a control animal became infected within 4 weeks, as evidenced by repeated isolation of HIV-1 from peripheral blood mononuclear cells and anamnestic antibody responses. The new experimental adjuvant has to be further investigated in other vaccine trials and different animal models.