Combined RNA and DNA Vaccination Strategy for Improving the Vaccine Immune Response
Felber, Barbara (NCI)
Pavlakis, George (NCI)
Pre-clinical (in vivo)
The development of an effective HIV vaccine has been ongoing. HIV sequence diversity and immunodominance are major obstacles in the design of an effective vaccine. Researchers at the National Cancer Institute (NCI) developed a novel vaccine strategy combining both DNA and mRNA vaccination to induce an effective immune response. This combination strategy could also be used to develop vaccines against cancer or other infectious diseases (ex. SARS-CoV-2).
Previous studies by NCI determined that regions of the polypeptides Gag and Env are both essential to the core structure and envelope of the HIV-1 virus. Co-administration of DNA expressing Gag and Env elicits a protective immune response and reduces infection burden. This current technology relates to earlier technology from the same inventors describing the identification of the conserved elements (CE) within HIV-1 p24Gag. Specifically, the inventors demonstrated that priming with p24gag CE followed by vaccination with either a full-length p55gag DNA plasmid or p24gag CE DNA together with full-length p55gag DNA increased the CE responses compared to vaccination with p24CE DNA alone.
The current invention expands upon the earlier technology, combining DNA and RNA vaccination strategies to induce an effective HIV immune response. The inventors demonstrated that administration of gag mRNA/LNP efficiently boosted both humoral and cellular responses in rhesus macaques previously immunized by a Gag DNA-based vaccine. Furthermore, the mRNA/LNP as booster vaccination induced more potent cytotoxic T cell responses than using mRNA as prime. Overall, this invention describes a heterologous prime/boost regimen including a DNA prime followed by mRNA boost vaccination with the same or similar immunogens – resulting in optimal levels of humoral and cellular immune response. The use of a mRNA booster to stimulate DNA primed immunity may be broadly applicable as a vaccination strategy for other infectious diseases and cancer.
Addresses key hurdle faced by current HIV vaccines: sequence diversity of HIV and immunodominance of specific epitopes
Induces optimal cellular and humoral responses
Reduces infectious burden
Potential vaccine strategy applicable to other non-HIV diseases, such as cancer
In vivo validation of vaccine strategy in non-human primates (rhesus macaques)
Prophylactic and therapeutic vaccines for HIV
Prophylactic and therapeutic vaccines for, infectious diseases
Prophylactic and therapeutic vaccines ,f or cancer