The development of an effective human immunodeficiency virus (HIV) vaccine has been an ongoing area of research. Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major obstacles by utilizing the combination of DNA and protein targets directed to the conserved HIV regions.
Previous studies by NCI have demonstrated that co-administration of DNA expressing Gag and Env proteins elicits a protective immune response and reduces infection burden. Env, which mediates virus host cell entry, has 5 variable (V) and 5 conserved (C) regions. Data from the RV144 HIV vaccine trial indicated that targeting the first and second variable region (V1V2) of Env, correlated with reduced risk of infection, making this V1V2 region an important vaccine target.
The NCI technology describes a method of priming with the scaffolded DNA that expresses the trimeric form of V1V2 scaffolded onto 2J9C, followed by boosting with the DNA that expresses the intact Env plus the Env protein. Preliminary in vivo results in macaques demonstrate that priming with DNA expressing V1V2, favored the development of V1V2-specific HIV antibodies upon initial vaccination and provided a head start for development of antibodies targeting V1V2. A booster vaccine, containing both DNA and Protein components, increased the magnitude of responses to V1V2 and induced the breadth of humoral response to other Env regions.
This vaccine strategy is also broadly applicable to non-HIV vaccines. As the method includes a prime to induce immune responses to an important target region, this is a key element to developing a successful vaccine.
Researchers at the NCI seek licensing and/or co-development research collaborations for this technology.
- Prophylactic and therapeutic vaccines for HIV infection
- Potential application to other viral diseases as this methodology constitutes a modality providing reduced risk of acquisition and better viral control
- Addresses two key hurdles faced by current HIV vaccines: sequence diversity of HIV and immunodominance
- Induces cross-clade cellular and humoral responses in terms of binding, mucosal targeting, neutralization, and effector functions while increasing affinity with each immunization
- Potential vaccine strategy applicable to other non-HIV diseases
- In vivo validation of vaccine strategy in non-human primates
Kulkarni V, et al. HIV-1 Conserved Elements p24CE DNA Vaccine Induces Humoral Immune Responses with Broad Epitope Recognition in Macaques. [PMID 25338098]
Singh S, et al. Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques. [PMID 29793957]
Hessell AJ, et al. Multimeric Epitope-Scaffold HIV Vaccines Target V1V2 and Differentially Tune Polyfunctional Antibody Responses. [PMID 31340151]
- U.S. Provisional: U.S. Provisional Patent Application Number 62/935,016, Filed 13 Nov 2019