The Use of mRNA for an HIV Envelope Vaccine (R43/R44)

The purpose of this Funding Opportunity Announcement (FOA) is to encourage Small Business Innovation Research (SBIR) grant applications from Small Business Concerns (SBCs) that will focus on the development of novel direct mRNA-based and self-amplifying mRNA-based HIV envelope vaccine platforms.  Such technologies should have commercial potential.

There is an urgent need for an HIV envelope immunogen component for use in HIV vaccine clinical studies.  Results of the RV144 vaccine clinical trial indicated that antibody responses to the gp120 B/E envelope proteins were the major components of the vaccine that contributed to the efficacy signal. 

In addition, the discovery of both broad and potent neutralizing antibodies against the HIV envelope in HIV infected individuals, provides additional evidence that the human immune system can respond effectively to the HIV envelope; therefore envelope immunogens could be the major component of an effective HIV vaccine. 

The use of mRNA-based vaccines expressing HIV envelope represents a very direct and rapid method to circumvent the manufacturing issues associated with viral, protein and DNA HIV envelope vaccines.  Specifically, the direct use of mRNA for immunization would eliminate the need to generate stable cell lines with modest expression and yield levels and the need to develop complex purification schemes, which appear to be specific for each new HIV protein-based envelope immunogen. Given the current time requirements and the associated GMP costs for protein-based HIV envelope vaccines, the manufacturing of RNA-based envelope vaccines would be significantly faster, less complicated and cost much less than protein-based envelope vaccines.  In addition, the exclusion of viral delivery systems would eliminate the concerns about pre-existing immunity to viral structural proteins.

This FOA will support highly innovative research to generate novel mRNA-based HIV envelope vaccine platforms, and/or improvement of existing mRNA platforms, focused on manufacturing and delivery areas such as:

• Improved yield of HIV mRNA manufacturing processes
• Development of HIV mRNA CGMP processes
• Improvement of HIV mRNA stability and protection of mRNA from RNAases
• Improvement of HIV mRNA delivery techniques and delivery sites
• Development of targeting strategies using synthetic or nanotechnologies (e.g., lymph nodes)
• Combination of HIV mRNA immunogenicity with mRNA encoding adjuvants
• Development of multi-immunogen and /or multi-clade HIV envelope mRNA vaccines
• Development of homologous or heterologous prime-boost vaccine
• Development and/or improvement of self-amplifying mRNA

Research areas not supported by this FOA:

• Viral delivery systems
• Non-envelope HIV RNA vaccines
• DNA vaccines alone without a RNA amplification mechanism
• Approaches proposing clinical trials (all phases)

It is important to emphasize that the topics listed above are only meant to be illustrative, and not a comprehensive list of appropriate topics, or exclusive of other appropriate topics. Applications may propose projects that are highly innovative or are enhancements of current approaches. In either case, studies should significantly advance the current state of the art and have commercial potential.

See Section VIII. Other Information for award authorities and regulations.