Annual and Interim Progress Report Summaries
Principal Investigator: David Ho
Project: Harnessing Dendritic Cells & Innate Immune Activation Signals to Guide HIV Vaccine Development
Submitted August 1, 2011
Drs. David Ho and Sandhya Vasan at the Aaron Diamond AIDS Research Center (ADARC) have successfully completed the first Phase 1 clinical trial of ADVAX, a DNA-based HIV vaccine candidate delivered with the TriGridTM in vivo electroporation system, manufactured by Ichor Medical Systems, in healthy volunteers. This study is completed and demonstrated that in vivo electroporation is safe, tolerable, enhances the cellular immunogenicity of ADVAX, and is dose-sparing. Ancillary immunogenicity studies indicate that ADVAX delivered by electroporation not only enhances the magnitude of cellular immune responses to this DNA vaccine candidate, but also its breadth.
Drs. Moriya Tsuji and Sandhya Vasan at ADARC have identified a promising new glycolipid-based vaccine adjuvant, 7DW8-5, which significantly enhances the immunogenicity of DNA and adenovirus-based vaccines. In partnership with the U.S. Naval Medical Research Center (NMRC), they demonstrated that this glycolipid-based adjuvant can boost the immunogenicity of an Ad5-based vaccine candidate in both mice and monkeys. Dr. Tsuji’s group is currently overseeing the design and conduct of formal audited manufacture, stability, and safety and toxicity studies of the adjuvant and antigen combination in anticipation of a Phase 1 clinical trial in humans next year.
Dr. Yaoxing Huang at ADARC has generated novel flagellin variants with increased binding affinity to the toll-like receptor 5 (TLR5) as a potential adjuvant strategy in HIV vaccine design. The highest affinity TLR5-binding variant was either co-administered with or fused to the HIV antigen p24 and tested in a mouse model to determine its adjuvanting capabilities. Indeed, these studies demonstrated potent adjuvant activity and significant dose-sparing effects in enhancing antibody responses against p24 in vivo. The significant enhancement of antibody responses induced by the TLR ligand-antigen fusion vaccines opens up a potential avenue for HIV-1 envelope immunogen designs aimed at inducing neutralizing antibodies in vivo.
Submitted July 30, 2010