HIV vaccine immunogen design to elicit broadly neutralizing antibodies

Existing viral vaccines provide immunity against a number of important infectious diseases. The technologies used to develop these vaccines generally work best against viruses that do not mutate very much in nature. However, conventional vaccine design approaches have proven inadequate for viruses such as HIV-1 that continuously evolve in order to evade our immune defenses. Thus, new vaccine design strategies are needed to tackle viruses like HIV.

Dr. Ralph Pantophlet’s research program is developing novel strategies for the design of vaccines that will induce broad immunity to HIV infection. Specifically, Pantophlet seeks to better understand molecular and immunological conditions that impact the elicitation of antibodies with the capacity to block the infectivity of a wide variety of HIV strains. This research focuses on these types of antibodies, dubbed “broadly neutralizing antibodies,” because of their demonstrable ability to block HIV infection in animal models. Another component of this program of research will be systematic studies to define neutralizing antibody target sites on HIV and investigate exposure of these sites at the molecular level. As part of the proposed research program, knowledge gained from the studies outlined above will be incorporated into the design of formulations to elicit target site-specific broadly neutralizing antibodies upon immunization. Thus, insight gained from this work is expected to advance HIV vaccine design efforts and be of significant interest to the field.

Although the focus will be on HIV, knowledge gained from this work may be applicable to other viruses for which conventional vaccine design approaches are also not optimal. Examples include hepatitis C virus, which like HIV is highly mutable and for which a vaccine has yet to be developed, and influenza, for which better vaccines are urgently being sought due to the constant threat of the emergence of a pandemic strain.

Keywords: HIV, vaccine, neutralizing antibody, immunogen design, vaccine immunology, B cell epitope, adjuvant, glycoprotein, T cell epitope, animal model