Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines

摘要

Highly pure preparations of recombinant gp120 were obtained from two different HIV-1 isolates. Conjugates of these HIV-1 gp120 proteins were prepared with tetanus toxoid (TT) and keyhole limpet hemocyanin (KHL) with the hypothesis that very immunogenic carrier proteins will induce better antibody responses to gp120. Conjugation procedures were selected that did not affect the ability of HIV-1 gp120 to bind to CD4. However, immunization studies in mice showed that anti-gp120 antibody levels were lower in animals immunized with conjugates compared with animals receiving HIV-1 gp120 alone. Moreover, repeated immunizations with either KHL-gp120 conjugates or gp120 alone failed to induce neutralizing antibodies to an HIV-1 clade B isolate. A combination of DNA vaccination and purified HIV-1 gp120 booster immunization was tested in baboons. The animals did not respond to the DNA vaccination, even in the presence of co- inoculated cytokines that are known to enhance the immune response. Only immunization with purified HIV-1 gp120 elicited a detectable, but short-lived, antibody response. Purified recombinant HIV-1 gp120 may not be the proper antigen for an effective vaccine against HIV-1.