The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy.
Researchers at the National Cancer Institute's Vaccine Branch used conserved elements (CEs) of the polypeptides Gag and Env as immunogenic compositions to induce an immune response to HIV-1 envelope polypeptides and Gag polypeptides. This invention is based, in part, on the discovery that the administration of one or more polypeptides comprising CEs, separated by linkers and collinearly arranged, of HIV Env or Gag CE proteins, can provide a robust immune response compared to administration of a full-length Env or Gag protein. The Env-CE DNA vaccines were tested in a rhesus macaque model and were able to induce a cellular and humoral immune response in this model whereas vaccination with the full length DNA did not produce the same effect.
A robust increase in immunity was observed when rhesus macaques were subjected to a prime-boost protocol. First, rhesus macaques were primed with Env-CE DNA and boosted with full length Env resulting in an observed increase in both the cellular and humoral responses. A further increase in immune response was observed from priming with CE and boosting with a combination of CE and full length DNA resulting in a significantly improved breadth of immune responses. These improved protocols may help solve the immunodominance problem observed in current protocols. This is considered a major obstacle for HIV vaccine development. The CE vaccines described by this invention have potential for use as prophylactic and therapeutic HIV vaccines.
- HIV vaccines
- Addresses two key hurdles faced by current HIV vaccines: sequence diversity of HIV and immunodominance.
- Induces cross-clade specific immune response.
- The prime-boost immunization regimen is not limited to HIV, but can be employed to improve the induction of immune responses to any subdominant epitopes (cellular or humoral) to increase breadth, magnitude and quality of the immune response.
Kulkarni, V. et al. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques [PMID: 24465991]
Kulkarni, V. et al. HIV-1 conserved elements p24CE DNA vaccine induces humoral immune responses with broad epitope recognition in macaques [PMID: 25338098]
- U.S. Provisional: US Provisional Provisional Application No. 62/161,123 filed 13 May 2015
- U.S. Provisional: US Provisional Provisional Application No. 62/241,599 filed 14 Oct 2015
- Foreign Filed: Foreign Filed Provisional Application No. PCT/US2016/032317 filed 13 May 2016