Genetic Adjuvants for RNA Vaccines
Abstract
Topic Area addressed by the proposed research project: Emerging Infectious Diseases. RNA vaccines can be developed and manufactured more rapidly than most traditional vaccines, making RNA vaccines promising tools for rapid responses to emerging infectious diseases. However, mirroring the level of protective immunity induced by many conventional vaccines is difficult. Adjuvants are immune-stimulating substances often added to vaccines in order to increase and diversify protective immune responses; thus, adding appropriate adjuvants to RNA vaccines may overcome reduced responses compared to traditional vaccines. We propose the development and testing of genetically adjuvanted RNA vaccines, in which key immune genes typically stimulated by traditional vaccine adjuvants are incorporated directly into the vaccine RNA itself. By directly stimulating immunity, we believe we can enhance RNA vaccine-induced immunity and mimic the comprehensive, durable responses induced by traditional live-attenuated vaccines. In this proposal, we will test these hypotheses using the re-emerging yellow fever virus as a model system. Yellow fever is an ideal model system for studies of immune responses to vaccination as YF-17D, the existing live-attenuated yellow fever vaccine, induces exemplary lifelong protective responses that have been extensively characterized both in laboratory animals and humans. We will start by characterizing the immune responses of mice to a self-replicating RNA-based yellow fever vaccine we previously constructed. We will then create a set of genetically adjuvanted yellow fever RNA vaccines candidates that add immune-stimulating genes to the vaccine, either individually or in combination. Finally, we will test these genetically adjuvanted vaccines’ ability to stimulate strong and long-lasting immune responses similar to the responses stimulated by the traditional yellow fever vaccine. Our project goal is to develop a method for adjuvanting RNA vaccines, which would allow RNA vaccines to induce durable and robust protection similar to that of the best traditional vaccines. Additionally, the vaccine platform developed as a result will allow for rapid development and manufacture of RNA vaccines against new disease threats. If successful, this novel approach establish a new standard for RNA vaccines and develop a set of tools for rapidly combating emerging infectious diseases and/or biological weapons.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110127
Entities
People
- Emily A Voigt
Organizations
- Infectious Disease Research Institute
- United States Army