Publications Archive

Natural immunity to HIV?

In recent years, tantalizing reports have been circulating regarding the possibility that some individuals who have been exposed to HIV were only transiently infected with HIV. Understanding the reasons why these people remain uninfected should shed light on the nature of protective immunity against HIV.

All infected people exhibit immune responses against HIV. One such response, production of antibodies against HIV, is diagnostic of infection. The problem is, these immune responses fail to provide protection against the virus, and people become sick despite being sero-positive (that is, having antibodies in their blood (serum) against HIV).

Some researchers have studied sero-negative persons who have been repeatedly exposed to HIV, because of the possibility that such people had successfully managed to fend off infection with an appropriate immune response. Had HIV established an infection, antibodies against HIV would have been present in their blood, yet the immune cells of some sero-negative people respond to HIV in test tube experiments as though the cells had encountered the virus before.

The antibodies made against HIV that are detected in the standard HIV test, belong to a class of proteins called immunoglobulin G (IgG). Antibodies are also produced at mucosal surfaces where transmission of HIV usually occurs, but unlike the IgG species of antibody present in blood, mucosal antibodies belong to a different class of protein called immunoglobulin A (IgA). IgA against HIV would not be detected in an HIV test. Some researchers believe that the immune responses most likely to protect against transmission of HIV are those that occur at mucosal surfaces. Could repeatedly exposed, yet uninfected, people have IgA against HIV?

Recently, a group of researchers in Italy headed by Dr. Mario Clerici examined a group of sero-positive individuals and their sero-negative partners for IgA against HIV. As expected, all sero-positive people had both IgG and IgA against HIV. The sero-negative partners had no IgG of course. The key finding is that these individuals expressed IgA antibodies against HIV. Furthermore, when several of the sero-negative partners were followed up one year following the cessation of "at-risk" sex, they remained sero-negative and their IgA levels were reduced.

One obvious conclusion is that these individuals were protected from HIV infection by virtue of high levels of IgA antibodies at their mucosal linings. In this model, one might imagine that those who remained sero-negative responded to HIV with a sufficiently potent IgA response. Those who become infected had an initially ineffectual or absent IgA response, and expressed copious amounts of IgA later (because HIV infection is active and chronic).

Remember that the individuals in this study were pre-selected, so that any genetic or biological attributes responsible for the protective immunity had also been pre-selected. In other words, the odds are very low that protective immunity would occur in any one individual; the researchers had defined a cohort that selected for the lucky minority.

However, one cannot jump to conclusion regarding cause and effect. It is possible that some other attribute or immune response conferred protective immunity on these sero-negative individuals. It is also possible that these individuals had been infected and that if one followed them long enough they would eventually exhibit signs of the infection (this possibility is less likely, but still plausible).

If mechanisms that protect people from HIV infection can be determined, this information might inform strategies for the development of a preventative HIV vaccine, and for controlling HIV in infected individuals.