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February 14, 2011

New Study Says HIV Vaccines Might Not Need to Produce Protective Blood Antibodies

A new study suggests that an HIV vaccine could protect against sexual transmission of the virus without producing protective antibodies in the blood—instead, the virus would provoke the body to produce mucosal antibodies in the vagina and rectum. These findings, published online February 10 in the journal Immunity, open up new avenues of HIV vaccine research.

Most traditional vaccines work in the same way: a killed, modified or fragmented version of an infectious organism is delivered to the body, prompting the immune system to quickly produce antibodies in the blood that are able to bind to and destroy the organism if it is encountered in the future. Vaccine research in HIV, however, has largely been a bust.

For one thing, scientists have yet to identify a naturally occurring model of protection against HIV, so it’s been difficult to figure out what types of antibodies would be most likely to protect people against infection. What’s more, even if we knew what types of antibodies were most desirable, we would also need to understand the required potentency of the antibody response (in other words, how many antibodies must be present in the blood) in order to protect against infection.

Now, however, a new study has turned that thinking on its head. Rather than focus on the production of antibodies in the blood, we should look at whether a vaccine can provoke the production of HIV-protective antibodies in the anatomical sites most commonly tied to infection—the vagina and the rectum—says Morgane Bomsel, PhD, from the Institute Cochin in Paris.

Bomsel and her colleagues were intrigued by documented cases where people have stubbornly resisted HIV infection despite repeated high-risk exposures—all without producing antibodies to the virus in the blood. In such cases, researchers found evidence of antibodies in mucosal tissue, specifically an antibody called IgG.

To determine whether a vaccine delivered intranasally (via the nose) or intramuscularly (via injections) could prompt the body to produce these mucosal antibodies, Bomsel’s team gave a gp41 vaccine to five macaca mulatta moneys and a placebo to six others. All of the monkeys were then exposed vaginally to the monkey version of HIV, called simian immunodeficiency virus (SIV), and followed for six months.

The results were in line with the researchers’ hopes. All five vaccinated monkeys failed to become infected with SIV, and all five produced both IgG in mucosal tissue as well as another mucosal antibody called IgA. Whereas the mucosal antibodies blocked a pathway that HIV uses to enter the mucosa, the antibodies in the plasma of these animals completely lacked the ability to neutralize the virus.

Meanwhile, all six of the monkeys who received a placebo became infected with SIV.

The authors caution that further study will be necessary to confirm their results.

“Our results clearly challenge the paradigm that mucosal protection requires significantly high levels of antibodies with virus neutralizing capacity in the blood,” said Bomsel in a release.

“These findings may help to explain why a small population of highly exposed, but HIV-negative, women who exhibit gp41-specific IgA in their vaginal secretions are protected from infection. We may have been able to recapitulate in a vaccine what a few individuals do naturally,” she concludes.

Search: Vaccine, gp41, antibodies, mucosal antibodies, IgG, IgA, SIV, Morgane Bomsel

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