Hunt for HIV vaccine a community effort

A number of people within the Brown community are conducting research to find a vaccine for HIV. GSJ writer Scott J. Turner takes a look at several of their efforts.
- Current vaccine trials
- "I feel like I am doing something for other people"
- Biology and behavior intertwine in HIV epidemic
- Attacking the HIV 'Achilles' heel'
- The road to Mali

Five years ago, President Clinton called for an HIV/AIDS vaccine within 10 years. If that goal is to be reached it will be because of the joint efforts of clinicians, researchers, community advisers and the people who volunteer for vaccine trials. That was the message Ken Mayer, M.D., shared during a recent gathering to celebrate the Fifth Annual HIV Vaccine Awareness Day.

“It’s not about pure science but about helping your community,” said Mayer, director of the Brown University AIDS Program.

Brown researchers conduct a range of HIV/AIDS vaccine trials out of the Immunology Center at The Miriam Hospital. That center is part of the Lifespan/Tufts/Brown Center for AIDS Research. The trials are part of a comprehensive effort by Brown faculty involved in research, teaching and education to prevent the spread of HIV/AIDS, said Mayer, left.

Three current vaccine trials are called Phase I studies. These are the initial tests of a drug in humans. Phase I studies look at a medication’s safety and tolerability among a relatively small number of individuals at low or no risk for HIV infection.

Initial vaccine trials present the most recruiting challenges, said Michelle Lally, M.D. The assistant professor of medicine oversees a total of five trials. Mayer is co-principal investigator for three of those.

“Early-phase trials are pivotal,” said Lally. “Making sure that a compound is safe to administer in healthy people at low risk paves the way for testing it in those at high risk of becoming infected with HIV.”

A typical concern among potential participants is that they will get the HIV virus from the vaccine. But that is impossible, Lally said. “The candidate vaccines contain, for example, just a piece of the outside envelope of the virus,” she said. “They’re analogous to a car without its engine.

Melissa DiSpigno is a registered nurse who helps run the studies and recruit subjects. “Eligible participants for Phase I studies must be healthy and at low- or no-risk for HIV infection,” she said. “It is those factors that allow us to test whether trial participants do or do not get ill from a vaccine.”

“Usually, participants … have known someone infected with HIV or really want to do something to help,” DiSpigno said. “People take part because they have it in their heart to want to do so.”

At last count, 74 people have participated in HIV/AIDS vaccine trials at The Miriam. “They are 74 heroes,” said Mayer.

HIV/AIDS is the deadliest plague in more than a century, and it continues to spread. Last year more than 5 million individuals worldwide were infected with HIV. Although there is no FDA-approved HIV vaccine, “a vaccine remains the best hope for stopping this epidemic,” said Lally.

Typically, vaccines work by encouraging antibodies to prevent infection. However, this method has not been fully effective against HIV. Moreover HIV can exist in several forms such as cell-free or cell-associated, Mayer said. And there are many HIV strains worldwide, he said.

Some candidate vaccines remain designed to encourage antibodies to prevent infection. Others are meant to boost the activity of killer cells in the immune system to kill cells containing HIV, but without harming healthy immune cells.

Brown researchers study both approaches. Their vaccine trials involve new drugs or different doses or blends of existing compounds; whatever shows potential.

Three current trials are funded by the National Institutes of Health through an international umbrella group of scientists, called the HIV Vaccine Trials Network (HTVN). Merck supports another, and a fifth is a later-phase study underwritten by the company VaxGen, in which high-risk patients have been randomized into an actual treatment or placebo.

The VaxGen study involves 5,400 people nationwide. Its results will be made known in February. “Our sense is that the vaccine will hopefully be somewhat effective, but we don’t anticipate that this will be ‘the vaccine,’” Lally said.

Brown researchers are also testing preventative vaccine candidates that may offer “partial immunity” to HIV/AIDS. “The hope is that these compounds may delay or prevent onset of AIDS in those infected,” said Lally.

“Such a vaccine would rev up the immune system to keep HIV under control,” Lally said. “Today if someone becomes infected, it might take 5 to 10 years for AIDS to develop. With one of these vaccines, it might take 20, or 30 or 40 years, or not at all.”

Vaccine trials, and all HIV/AIDS preventative research efforts, are the products of “an incredibly dedicated staff and wonderful volunteers,” said Mayer.

For information on participating in one of the vaccine trials, call 793-4335.

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When Karen Lembo’s buddy Steve (a pseudonym) told her that he was HIV positive, she didn’t let their friendship drift. When Steve said that he was fed up with the side effects of his drug regimen and dispirited by the deaths of so many friends, Lembo listened.

Then last year, Steve complained that society didn’t really care about those infected with HIV or those who had developed AIDS. But Lembo showed him otherwise. She enrolled in an HIV/AIDS vaccine trial at The Miriam Hospital.

“He said that it was awesome, and such a great thing that I was doing,” she said. “Someone has to do something. [The trial] doesn’t hurt my life and I feel like I am doing something for other people.”

Lembo, 37, is taking part in a trial to test a potential vaccine’s safety and tolerability. The trial involves a relatively small number of individuals at low risk or no risk for HIV infection. Healthy and non-HIV-positive, Lembo is one of four people in Providence currently enrolled in the placebo-controlled 18-month investigation.

A single mom who juggles two jobs, Lembo learned about the trial via an advertisement in the Providence Phoenix. Over a five-month period, she received a total of three injections and has been closely monitored by hospital staff.

Lembo said she is “enthusiastic” about the opportunity and “encouraged” by the vaccine hunt. She urges others to get involved.

“If we can help each other that’s good,’ said Lembo. “People may be scared of AIDS but people need to think more about AIDS. The more people get we get for these studies, the easier it will be to come up with a vaccine.”

Participation in the trial has reinforced in Lembo the use of commonsense protection from HIV and other sexually transmitted diseases. She practices safe sex and urges other to do the same.

“I hear people say that HIV and AIDS only affect gay men and drug users. But that is not true,” she said. “I hear people say that we don’t have to protect ourselves because new drugs take care of infection. That is not true either.

“People must protect themselves. If you get HIV, it’s not nice, it’s not good and it’s not going to go away.”

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When it comes to fighting the spread of HIV, you cannot separate the biological from the behavioral, said Kenneth Mayer, M.D., a professor of medicine and community health who has studied HIV/AIDS for more than 20 years.

HIV is most commonly spread through heterosexual sex but is also spread through other activities such as the exchange of dirty needles. From finding and testing an HIV/AIDS vaccine to establishing the value of needle-exchange programs to improving condom use, more than a dozen Brown faculty members take part in a comprehensive program of research, teaching and community education that address both the biological and the behavioral factors behind the spread of HIV. Their work takes place locally, nationwide and abroad.

Mayer heads the Brown University AIDS program. Among his research efforts is a close look at microbicides – topical gels designed to prevent vaginal transmission of HIV. Condoms may prevent HIV transmission but women usually cannot get male partners to use condoms correctly.

“Microbicides may be considered ‘chemical condoms,’” said Mayer. They are based on the behavioral concept “that lubrication around sex is very common and socially acceptable, and that HIV often enters the body via mucous membranes. Lubrication is something that either a man or a woman can apply, either during heterosexual or homosexual sex, and which can even enhance sexual pleasure, he said.

“With microbicides, we give women the means to protect themselves while waiting for a vaccine,” Mayer said. “Microbicides also provide a chance for protection for people who cannot or will not reduce high-risk behaviors.”

There are several “interesting microbicidal candidates,” Mayer said. They may stop HIV from bonding to cells, interrupt the HIV life cycle or keep the vagina acidic, which interrupts HIV’s ability to multiply. A few compounds may also protect against other sexually-transmitted diseases.

Last month, Mayer and colleagues began a new trial to study the safety of an experimental topical gel using the antiviral compound Tenofovir – also known as PMPA – which is the active ingredient in an oral HIV/AIDS drug approved by the Food and Drug Administration. Lab tests show that Tenofovir is a potent inhibitor of many drug-resistant strains of HIV.

“We can’t wait for the perfect vaccine without acting,” Mayer said. “That is why we conduct multidisciplinary research to stem the tide of HIV infection while we search for that perfect vaccine.”

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Anne DeGroot’s effort to create and distribute at little or no cost a globally effective AIDS vaccine received a shot in the arm earlier this month when she received a $2.7-million grant from the National Institutes of Health to fund lab work needed to develop that vaccine.

The award will support studies in genetically modified mice as models of the human immune system to test initial response to a vaccine designed to prevent the spread of HIV/AIDS worldwide. Forty million people around the world are infected with HIV.

An assistant professor of community health and director of Brown’s TB/HIV Research Lab, DeGroot, a medical doctor, is also president of the vaccine design firm EpiVax and founder of the nonprofit GAIA Vaccine Foundation.

For six years. DeGroot and colleagues have worked to design an AIDS vaccine based on the global variability of the HIV virus and tailored for world regions devastated by the disease.