Session Day and Time: Wednesday 1:30 - 3:30 pm
Room: Hall D
Background: Current HIV vaccine candidates elicit reasonably potent cellular immune responses, but only low levels of neutralizing antibodies. Such CTL based vaccines (e.g., those based on DNA immunization) do not prevent infection, but can have a beneficial effect on disease course. In contrast, passively infused antibodies can provide complete protection, but high antibody levels are required. In order to assess if CTL could combine with antibody to produce sterile immunity, we studied the effect of a sub-optimal dose of neutralizing antibodies in animals with active immunity induced by IL2-adjuvanted DNA immunization. Based on prior vaginal challenge studies, the dose of antibody was calculated to be just below the threshold amount needed to provide sterile protection.
Methods: Twenty (20) female macaques were divided into 4 groups of 5 animals: 1) DNA immunization plus irrelevant antibody; 2) DNA immunization plus infusion of MAbs 2F5/2G12; 3) sham DNA plus MAbs 2F5/2G12; and 4) Sham DNA and irrelevant antibody. DNA immunization was performed with plasmids encoding the SIVmac239 Gag and the HIV-JRFL Env, and monkeys were challenged by vaginal exposure to SHIV89.6PD. Challenge was performed 14 weeks (wks) after the 4th DNA immunization (24 hrs after antibody infusion). All DNA immunized monkeys developed robust CD8 specific T-cell responses measured by epitope specific tetramer staining and by pooled peptide ELISpot assays for gamma-interferon secreting cells.
Results: After vaginal challenge, all 5 control animals, and all 5 DNA immunized animals, became infected. Over the course of 24 wks, the DNA immunized animals displayed lower viremia and higher CD4 T-cell counts than control animals. Among the 5 animals that received only infused antibody, 2 displayed no plasma viremia and appear to be completely protected. The results were similar for the group that received both DNA immunization and infused MAbs; 2 animals appear to be completely protected.
Conclusions: While DNA immunization produced robust primary and secondary HIV-specific CD8 T-cell immunity, and ameliorated disease course, we were unable to demonstrate that pre-existing cellular immunity contributed to the sterile protection mediated by antibody infusion.