E-102 Advances in Prophylactic HIV Vaccine Development

Abstract

The RV 144 HIV vaccine trial in Thailand demonstrated that a preventive HIV vaccine was possible with early efficacy estimated at 60% which waned over time coincident with non-durable vaccine evoked immune responses. New insights into correlates of risk of infection are focused on the C1 and V3 regions of Env as well as V2 with IgG subclass 3 and antibody dependent phagocytosis and other non-neutralizing antibody mechanisms of action. Late boosts of RV 144 vaccinees are demonstrating the evolution of neutralizing antibodies whose extent of somatic hypermutation and CDR3 length are promising for planned follow-on efficacy studies in Africa and Asia. Associations between host HLA class II genes and transcriptional profiling have yielded new insights into correlates of risk of infection. The rational for next generation rare serotype adenoviral vectored HIV vaccines with trimer Env boosting continues to be strengthened in data derived from coordinated non-human primate studies. New adjuvant systems are being explored to build on these insights and to extend the durability of evoked relevant immune responses.