October 25, 2010

HIV Antibodies Do Control Infection: New Hope for Vaccines and Treatment

B-cells and neutralizing antibodies (NAbs) might control HIV levels better than scientists previously suspected, according to a single-patient study reported in the October issue of Nature Communications. The intriguing finding, the authors note, could open a new avenue for both preventive and treatment vaccines for HIV.

B-cells and antibodies represent an important arm of the immune system. When a vaccine is administered, it provokes the body into producing antibodies against a specific disease-causing microbe; that way, a vaccinated person exposed to the microorganisms will be protected. Therapeutic antibody vaccines are used for people already infected with a particular disease; in these cases, the vaccines help them control the infection.

Unfortunately, numerous vaccine studies have suggested that neutralizing antibodies don’t help prevent HIV infection. They also don’t appear to help control HIV disease progression very much once a person is infected.

To add a new perspective on the subject, Kuan-Hsiang G. Huang, PhD, and his colleagues from Oxford University in Oxford, England, had the unique opportunity to study for the first time the direct impact of B-cell and NAb levels on the control of HIV. This was possible because they had a patient who was HIV positive, not on antiretroviral treatment and had to have his B-cells depleted with chemotherapy to treat B-cell lymphoma. That he did not require treatment to control his HIV suggests that some immune mechanism was actively suppressing the virus.

The participant was 58 years old when he came down with symptoms indicating that he’d been recently infected with HIV. Three years earlier, he had been diagnosed with B-cell lymphoma, but the disease was mild enough that he did not require treatment. He was also previously infected with hepatitis B virus (HBV), but that disease was also not active. About 30 months after his HIV diagnosis, his lymphoma began to worsen, and he received Rituxan (rituximab). This treatment works by killing off B-cells.

About five months after starting Rituxan, the participant reported feeling unwell, with fevers and malaise. It was found that his HIV viral load had significantly increased, jumping from undetectable to more than 700,000 copies, and that his HBV infection had been reactivated. At the same time, he had a decline in B cells and a corresponding decline in neutralizing antibodies.

After he completed Rituxan therapy, his B cells and NAbs began to rebound, and shortly thereafter, his HIV levels returned to undetectable. In response to this finding, Huang and his colleagues commented that the increase in NAbs was tied to a reduction in HIV: “There is a clear relationship between the changes in NAb [levels] and [HIV levels] demonstrated in this study.”

It is possible that the reactivated HBV infection—which is known to occur during Rituxan therapy—could have been the reason the man’s HIV levels rose, and not the reduction in NAbs. The authors stated, however, the participant’s HIV levels became undetectable again quickly and spontaneously after NAbs began to rise, and that this drop occurred despite HBV levels remaining high.

The authors concluded: “This unique study suggests that B cells, and their secreted NAbs, can affect HIV viral load in chronic infection. This evidence, derived directly from observations in man, may inform the rational design of future immunotherapies and HIV vaccines.”

Search: B-cell, antibody, neutralizing antibody, NAb, hepatitis B virus, HBV, Kuan-Hsiang G. Huang

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Previous Comments:

mike, , 2010-10-27 20:59:57
can some one please tell me is there a better meds than atripla which is one a day, today in the market? thank you

LynnS, MO, 2010-10-26 23:23:33
Credit to these guys for think about this. Enough minds together will overcome!

Richard Jefferys, , 2010-10-26 18:49:44
Just to follow up, the paper (which is open access) does explicitly discuss the possibility of an impact on T cell function, the authors feel the change in viral load should have been faster if it was caused by T cell responses. There's also some info suggesting mutations in the virus due to an anti-HIV effect of the antibodies.

Richard Jefferys, New York, 2010-10-26 10:24:17
The finding may not actually be related to antibodies, which are rarely able to mediate significant anti-HIV activity. B cells also have a role in generating and sustaining T cell responses, so depleting B cells may impact viral load control by impairing HIV-specific CD4 T cell and CD8 T cells.

tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2009/02/a-role-for-b-cells-in-the-development-of-cd4-t-cell-memory.html