Conventional vaccines such as live attenuated and killed virus fail against the highly variable and evasive HIV. Our approach is based on the induction of broadly neutralizing antibodies (bnAbs) to the envelope trimer (green) on the surface of the virus.
Env houses the machinery that allows HIV to infect cells; it is the sole target of bnAbs.
At the heart of difficulty in eliciting bnAbs is the nature of Env, which is a compact protein structure highly decorated with sugars (purple) and difficult for Abs to recognize. We have determined the molecular structure Env and have defined the sites on Env recognized by bnAbs in molecular detail. These studies have facilitated the precise design of our vaccine candidates.
They are antibodies able to neutralize (inactivate) a large proportion of global circulating HIV strains. They arise in some HIV-infected individuals usually after several years of infection. Through encounter with many different viruses (immunogens) antibodies evolve to recognize a variety of shapes exhibited by distinct viral strains.
The challenge, and essence of the bnAb approach to HIV vaccine design, is then to generate bnAbs in HIV-uninfected humans. We do not have the luxury of presenting many different immunogens over several years. In vaccination, we must present a manageable number of immunogens over a limited time period.
We propose a rational vaccine design strategy in which a small number of well-designed immunogens are used in sequence. Immunogens are designed based on molecular level understanding of the interaction of bnAbs with the virus and on the biology of Ab responses.
Equally important is the optimization of immunization strategies. We vigorously pursue novel immunogens and immunization strategies in pre-clinical models with the aim of bringing them into the clinic as soon as possible to yield an HIV vaccine.
Additionally, we emphasize that each immunogen that enters clinical studies should test key hypotheses in our overall strategy.
The CHAVD has 26 Principal Investigators working on different aspects of designing and evaluating an HIV vaccine across the US and the World. The CHAVD is led by Dr Dennis Burton at The Scripps Research Institute in La Jolla, California.Download PDF
We have worked together extremely well as a team, as evidenced by our 142 high-profile joint manuscripts, but also by our successful collaborations. Those collaborations and partnerships facilitate the staged process during which we proceed from Ab and Env discoveries through immunogen design to animal testing and ultimately to the clinic.Download PDF
We have a rich pipeline of highly innovative vaccine concepts that progress through early laboratory design, preclinical testing, iterative design, GMP manufacturing, and eventually human Phase I trials. We continuously prioritize and re-evaluate our candidates, discarding designs that fail at critical junctures, and advancing only the best-in-class vaccine product candidate with convincing preclinical evidence.Download PDF