Zeroing In on An HIV Vaccine

CORRECTION APPENDED

By identifying a novel potential target for treatment, Harvard scientists may have brought us one step closer to finding a vaccine for HIV.

A recent paper from Harvard Medical School and the Dana-Farber Cancer Institute proposes a mechanism by which “broadly neutralizing antibodies” (BNAs) can block an HIV infection. The paper is published in the January issue of Immunity magazine.

Many scientists have attempted to find HIV vaccines in the past and most of their efforts have focused on protecting T-cells, the antibody-producing cells that HIV kills. However, according to Medical School Professor Ellis L. Reinherz ’71, scientists have yet to discover a way to keep HIV from developing in patients. [SEE CORRECTION BELOW]

In the recent study, Reinherz and his colleagues probed how an antibody might disrupt HIV and prevent it from entering human cells in the first place.

Reinherz, who is faculty director of the Cancer Vaccine Center at Dana-Farber, said he hoped that such an antibody would be a valuable tool in the fight against HIV.

“Antibody and T-cell eliciting vaccines may work even better together.” Reinherz said.

The researchers examined a region on the surface of HIV that is consistent across many strains of the virus: the membrane proximal ectodomain region (MPER).

They used nuclear magnetic resonance and other imaging techniques to study the structure of this region, which is partially imbedded in the viral membrane.

According to Reinherz, after mapping MPER, the team tested their findings using a particular BNA called 4E10. They found that 4E10 was able to pull portions of MPER out of the viral membrane and attach itself to the virus. The antibody then prevents the viral membrane from fusing with the membranes of human cells, effectively blocking HIV infection.

Understanding how such rare antibodies as 4E10 function may shed light on why they are not regularly produced by the body, as well as how they may be induced to activity.

Barton F. Haynes, director of the Duke Human Vaccine Institute and the Center for HIV-AIDS Vaccine Immunology, said that the authors of this paper present key information about how HIV hides MPER from human antibodies.

“They figured out which pieces of the envelope the antibodies latch onto, and that’s a clue for designing something synthetic that you could give to people to stimulate the development of these antibodies,” he said.

According to Haynes, however, some important questions remain unanswered, including how neutralizing antibodies interact with HIV in the body.

Reinherz also said that there are several necessary steps remaining before the research can be turned into a preventative treatment.

The study’s lead authors are Mikyung Kim of Dana-Farber, Zhen-Yu Sun of the Medical School, and Kyung Joon Oh of Dana-Farber and the Medical School. The co-authors are Jessica Yu and Vladimir Brusic of Dana-Farber; Likai Song, Zhisong Qiao, and Jia-huai Wang, of Dana-Farber and the Medical School; and Gerhard Wagner, of the Medical School.

—Staff writer Sue Lin can be reached at suelin@fas.harvard.edu.

For recent research, faculty profiles, and a look at the issues facing Harvard scientists, check out The Crimson's science page.


CORRECTION

Due to an editing error, the Feb. 7 story, "Zeroing in on an HIV Vaccine" described T cells as being "antibody-producing." In fact, antibodies are produced by B cells, which, in turn, are stimulated by T cells.