Antibodies Meet Microbicides

Using a laboratory model made from post-surgery cervical and colo-rectal human tissue, researchers at the University of Pittsburgh Graduate School of Public Health are seeing positive initial results in HIV prevention by adding powerful antibodies to a topical gel.

The Pittsburgh experiments bring together the intriguing concept of deploying antibodies, which can neutralize many different strains of HIV, along with the convenience of a topical, microbicide gel. Recent successes in testing HIV-preventive microbicides made them a hot topic of discussion this week in Cape Town, South Africa, where Yanille Scott outlined her results.

Scott, a doctoral fellow at the McGee Women’s Research Institute who works with the Pittsburgh-based Microbicide Trials Network, says adding neutralizing antibodies to a temporary-acting topical gel is different from the idea of passive transfer, where antibodies are injected systemically, but it’s not a radically different notion.

“It’s something of a different perspective,” she says. “As opposed to passive transfer, it would not be expected to have a long residual effect. After a few hours it would wear off. Just like you would use a lube,” Scott says.

Initial results with this strategy are encouraging, she reports. Results vary depending on the type of antibody; Scott tested the neutralizing antibodies PG16, PG9, VRC01, and 4E10. Also, the team discovered much less antibody is needed to achieve a protective effect using rectal tissue than in cervical tissue.

“We take cervical tissue or colo-rectal tissue from people who have undergone colon resections or women undergoing routine hysterectomy for non-inflammatory conditions,” she says. “Within a few hours of surgery, they’ll call us, we’ll go pick it up, we set it up, we activate the tissue so all the immune cells are alive and active and we know that something is going on.”

The team then treats the tissues topically with the neutralizing antibody and adds the virus. “We’ve used the virus in medium and virus in semen, modeling HIV-infected semen.”

Scott observed protection levels of 90%, 100%, 80%, and 30%, respectively, with the neutralizing antibodies PG16, PG9, VRC01, and 4E10. The first three offered 100 percent protection of rectal tissue, with 4E10 again lagging, this time at 50%.

Scott says the results show at the very least that topically applied antibodies are effective in the presence of semen, and that this approach should be considered for HIV prevention. An antibody gel could also be used for HIV-infected people to cut down the risk of transmission to their partners. “We’re trying to understand exactly what this model is telling us and to know exactly what we can do with the data in terms of developing an antibody microbicide.”  – Michael Dumiak