Ho: Enhancing Innate Immune Activation
The Ho-led research consortium is exploring ways to enhance immune activation upon vaccine administration. Dendritic cells (DCs) are a type of immune system cell involved in the body’s innate response to pathogenic invaders. These cells ingest viral particles and display bits of them on their surfaces so that other immune cells, such as T-cells, can mount immune responses to the viruses. The Ho-led team is studying various approaches to harness the power of these dendritic cells to improve vaccine immunogenicity both in pre-clinical and clinical research efforts.
The Ho-led research team is pursuing several distinct vaccine approaches to direct HIV-1 antigens to dendritic cells or induce type I interferon that can recruit and mature DCs. Each of these vaccine approaches has a modality to mature DCs, either co-administered exogenously or built-in.
The team is also developing both a novel vaccine adjuvant and a novel vaccine delivery platform. The adjuvant is a glycolipid compound that stimulates natural killer T cells, leading to DC maturation and improved immune responses to vaccines. In a parallel effort, the TriGridTM in vivo electroporation device improves the immunogenicity of DNA-based vaccines by increasing the amount of vaccine delivered to cells.
These product development activities entail studies ranging from in vitro construction and characterization to animal experimentation, and to pilot human trials for select efforts.
In previous years, researchers at the Aaron Diamond AIDS Research Center (ADARC) have reported results from 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. Strong positive results indicate 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.
In the past year, researchers have continued preclinical development of a promising new glycolipid-based vaccine adjuvant, 7DW8-5, which significantly enhances the immunogenicity of DNA and adenovirus-based vaccines in animals models. In partnership with the U.S. Naval Medical Research Center (NMRC) and the Tulane National Primate Research Center (TNPRC), we demonstrated that this glycolipid-based adjuvant can significantly boost the immunogenicity of an Ad5-based vaccine candidate in monkeys without causing evident systemic reactogenicity. Clinical development plans for ADNY003 (the glycolipid adjuvant, 7DW8-5, in combination with the Ad5-based vaccine candidate, AdPfCA) were presented to the US FDA in a Pre-IND meeting earlier this year, and ADARC is currently engaging in GMP-manufacture of 7DW8-5 and preclinical toxicology studies of ADNY003 in anticipation of a Phase 1 clinical trial that will begin enrollment at the end of next year.