Promising leads opening up with vaccine research
Promising leads opening up with vaccine research
One route involves neutralizing antibodies
The recent positive news from the Thailand HIV vaccine trial comes at a good time for the field as scientists recently have discovered other interesting potential ways to prevent infection from taking hold.
"Even without the Thai trial results there are other exciting things going on in vaccine research," says Alan Bernstein, OC, PhD, executive director of the Global HIV Vaccine Enterprise in New York, NY.
For instance, researchers at the International AIDS Vaccine Institute (IAVI) of New York, NY, have discovered two new broadly neutralizing antibodies to HIV.
"It's certainly very exciting," says Pat Fast, MD, chief medical officer of IAVI.
"We believe for a vaccine to work well it will need neutralizing antibodies," Fast explains. "The ideal vaccine that would protect everyone completely against infection would need neutralizing antibodies against HIV."
With HIV, it's very difficult to locate strong neutralizing antibodies because even people with HIV infection often do not have strong or broad antibodies, she notes.
"But if you had a vaccine, and you don't know which viruses a person will encounter you need that broad neutralization," Fast explains. "So we decided to search for people around the world who made very strong neutralizing antibodies and enter them in a study to see what exactly it is in the virus their antibodies interact with."
The goal is to mimic the exact shape the antibodies react to and put that into a vaccine, she adds.
"So we found 1,800 people who'd been infected with HIV for at least three years and who had really good antibodies," Fast says. "We took some blood cells from those volunteers and sent those to a company named Theraclone [Sciences in Seattle, WA] who cloned out the antibodies."
This method produced antibodies that were 100 times stronger and considerably broader than anything studied so far, she adds.
Also the broadly neutralizing antibodies discovered are associated with a strain that is infecting people in the developing world, while previously discovered antibodies were associated with a strain circulating in the Americas, Europe, and Australia.
Targeting Africa and Asia
IAVI researchers are focusing on developing a vaccine that would be effective in Africa and Asia because these are the regions where the vaccine is most needed, Fast says.
"We're hoping this research gives us insights that will allow us to make a vaccine," she adds.
The next step is to see if those antibodies can recognize the virus and then be incorporated into vaccine design, Bernstein says.
"We'll triage our own immune system to make those antibodies before we're infected with the virus," he explains. "That's the rationale for wanting to have those antibodies, and it's very exciting work."
University of California at Santa Cruz researchers are trying to develop better vaccine antigens to more broadly utilize antibody responses.
One approach makes use of natural HIV variations, which occur in each infected individual, says Phillip Berman, PhD, chair of the department of biomolecular engineering in the school of engineering at the University of California - Santa Cruz. Berman also is the Jack Baskin professor of biomolecular engineering.
The goal is to identify epitopes and identify mutations that allow viruses to escape the immune response, Berman says.1
"The first thing we discovered was this novel hydrogen-bonded ring structure in the part of the HIV envelope protein that mediates viral fusion and entry into cells," he adds. "The antibodies we hope to make will provide better exposure of the sites recognized by neutralizing antibodies, which we think normally are hidden within the molecule."
Another important line of work involves investigation into the mechanics of what happens in HIV infection for long-term nonprogressors, Bernstein says.
"There are about 100 or 200 people [they're aware of] who are able to naturally control the virus," he says. "So how do their bodies work and what's going on?"
So far, clues suggest there's something different about their immune systems.
"So the question comes up: Can we exploit that information and incorporate it into vaccine research?" Bernstein says.
In the spring of 2010, there are plans to publish a global scientific strategic plan for the vaccine research field, Bernstein notes.
"One of the themes emerging is the need for the field to start encouraging new people from other fields to work on HIV vaccine research," he explains. "I think these recent positive results are real reasons for optimism and will encourage funders, young people, and scientists from other areas to come into this field."
The key is collaboration between nations, scientists and scientific fields, and HIV organizations, Bernstein says.
"I do believe the HIV vaccine is solvable," he adds. "It's a wonderful opportunity for governments all over the world to step up to the plate and help us go from 30% vaccine success to 100% success."
Reference
- O'Rourke, Schweighardt B, Scott WG, et al. Novel ring structure in the gp41 timer of Human Immunodeficiency Virus Type 1 that modulates sensitivity and resistance to broadly neutralizing antibodies. J Virology. 2009;83(15):7728-7738.
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