HIV Peptide Conjugated to Heat-Killed Bacteria Promotes Antiviral Responses in Immunodeficient Mice

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Abstract
Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4+ T cells. The MHC class H-deficient mouse (II−/− environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4+ T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Bruceila abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-–A, but not the T-dependent antigen V3-–LH, induced high levels of IL-12, IFN-yγ and IL-10 mRNA in both wildtype (WT) and 1II−-−mice within 24 hr of injection. V3-–A-treated, but not V3-–LH-treated, 1II−-−mice developed serum IgG and IgA anti-V3 antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-–A in II−-−mice were capable of neutralizing HIV. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients.