HIV vs. the Immune System: Early Viral Mutations May Hold Clues for Vaccine Development

By Rowena Johnston, Ph.D.

Dr. Morgane Rolland

November 15, 2010— In the battle between HIV and the immune system, the virus has proved to be an elusive foe. HIV’s ability to mutate frequently—which produces a wide variety of different viral strains even in a single individual—means that the immune system can almost never pin down a stable target to destroy. This viral variation results in the failure of the immune system to clear HIV infection and is also reflected in the inability of scientists, so far, to identify any stable, immutable regions in the virus that a vaccine could be designed to target.

Because a vaccine is generally intended to stop infection before it can be established, amfAR Krim Fellow Dr. Morgane Rolland and associates, writing in the October issue of the Journal of Infectious Diseases, reason that a more comprehensive characterization of the genetic variability of the virus, focused around the time of infection, could form the cornerstone of the most effective AIDS vaccine. After all, it is the viruses present during the earliest days of infection that must be targeted and destroyed in order to prevent the establishment of infection.

Dr. Rolland and her colleagues note the recent discovery that in the great majority of sexual transmission cases, HIV infection appears to be founded on a single viral genetic lineage. While this seems at first glance to be good news—a vaccine may have to be effective against only a narrow range of genetic variability—so far researchers have not been able to identify any shared characteristics of these founder viruses that would permit more specific vaccine targeting.

To design an effective vaccine, it will be critical to understand how the interplay between the immune system and the virus contributes to the mutations that make controlling the virus progressively more difficult. Recent technological advances have revealed that the immune system begins to exert considerable pressure on the virus earlier in infection than had previously been suspected, as early as 17 days post-infection. The immune system forces the virus to mutate into variations of itself to escape destruction by killer T cells, but so far there are not sufficient data to know whether the virus mutates in predictable and similar ways in different people during these earliest stages of infection—ways that could be targeted by a vaccine.

For the virus, there is a catch to all this mutating: resulting viruses may be significantly less capable of replicating than their forebears, and there are some regions of the virus that cannot tolerate any mutation. This phenomenon may in fact be linked to the ability of a very small number of people, known as elite controllers, to control virus levels without the use of antiretroviral therapy. There is some speculation that the immune responses of these individuals may force the virus to mutate in ways that reduce its potency.

Rolland and her colleagues suggest that further study of the nature of the virus that first infects people, as well as the earliest immune responses that govern how the virus replicates and mutates, can help us understand not only the disease course that ensues, but also how infection can best be controlled, or even eliminated, by a vaccine.

Dr. Johnston is amfAR’s vice president and director of research.