HIV PEPTIDE CONJUGATED TO HEAT-KILLED BACTERIA PROMOTES ANTIVIRAL RESPONSES IN IMMUNODEFICIENT MICE

Enhancement of immunity in the setting of HIV infection is difficult o wing to loss of functional CD4(+) T cells, The MHC class II-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 opportunisti c infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses, V3-BA, but not the T-dependent antige n V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in b oth wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-tre ated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA a nti-V3 antibodies, with IgG(2b) and IgG(3) as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, dem onstrated that the antibodies generated by V3-BA in II-/- mice were ca pable of neutralizing HN. These experiments demonstrate that a heat-in activated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing a ntiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HI V-1 patients.