HIV vaccine research requires unprecedented path, expert suggests

Dr. Fauci explains that certain immune cells (B cells) typically produce neutralizing antibodies (NAbs) to most viruses within days or weeks of infection. These NAbs allow the infected person to clear that viral strain and enjoy lifelong immunity. This principle is used to create most viral vaccines, in which the killed or weakened virus itself or selected immunogens--benign components of virus -- are used to induce the production of NAbs without establishing an infection. People infected with HIV, however, do not readily produce Nabs and when they do, they are not produced in sufficient time to clear or even control the infection. Because of this, efforts to vaccinate individuals with HIV immunogens and coax their immune systems to establish protective NAbs have not yet been successful.

To overcome these difficulties, HIV vaccine researchers employ methods and technologies rarely seen in other branches of vaccine research, such as rigorous analyses of the B cell repertoire and its evolution and sophisticated structural biological techniques that determine precise molecular conformation of viral components and their interaction with NAbs. Dr. Fauci writes that the breadth and diversity of efforts to establish broadly neutralizing HIV antibodies in the absence of infection will be remembered, if successful, as the most elegant and complex approach toward the development of a vaccine in history. If unsuccessful, these efforts will offer comprehensive evidence that it will be unlikely that a vaccine will be able to induce broadly neutralizing antibodies. Hopefully, the former and not the latter will be the case.