In HIV-1 infected individuals, CD4-bearing T cells, are functionally deficient early in the course of the infection, and become numerically depleted in advanced stages of the disease. In devising a strategy for vaccinating HIV-1 infected individuals and/or boosting their memory B cells to produce high titers neutralizing antibodies, we looked for means of producing relatively T-helper cell Independent immunogens. We made progress in two parallel approaches: I. We tested the ability of the bacteria Brucella abortus (Ba) in an inactivated form, to serve as a carrier for inactivated HIV-1 virions. HIV-1-Ba conjugates as well as unconjugated HIV-1 were used to immunize Balb/C mice. The HIV-1-Ba conjugates generated faster and higher titers of anti-HIV-1 antibodies compared to the unconjugated HIV-1 virions.The antibodies generated by the HIV-1-Ba conjugates were predominantly of the IgG 2a+2b classes. They were effective in neutralizing HIV-1 env mediated syncytia formation. Furthermore, immunization of CD4-T cell depleted mice with the HIV-1-Ba (but not with the unconjugated HIV-1), resulted in the generation of syncytia blocking IgG antibodies. II. We tested the ability of a polymer consisting of repeating CD4-derived peptide units, to generate IgG responses in normal and in T cell depleted nude mice. In normal mice, both control peptide-KLH conjugate, and the polymeric peptide gener- ated IgG responses. In contrast, in the T-cell depleted nude mouse model, only the polymeric peptide generated IgG antibodies which recognized native CD4 on western blots. These two approaches are currently tested using HIV-1 envelope derived peptides from different conserved regions of the envelope. We hope to produce relatively T cell-independent vaccine which will generate IgG antibodies with multiple-strain neutralizing activities.
