New research boosts HIV vaccine quest
Following proteins down the rabbit hole
Scientists have discovered two potent human antibodies that can neutralize more than 90% of known global HIV strains from infecting human cells in the laboratory, and they have demonstrated how one of these disease-fighting proteins achieves this action.1,2 Such antibodies might be used to design improved HIV vaccines, researchers say.
Finding individual antibodies that can neutralize HIV strains anywhere in the world has been difficult due to the virus' capability to develop surface proteins to evade recognition by the immune system. As a result, several HIV variants exist worldwide.
However, researchers have identified a few areas on HIV's surface that remain nearly constant across all variants. One such area, called the CD4 binding site, is located on the surface spikes used by HIV to attach to immune system cells and infect them. By using their knowledge of the structure of the outer surface of HIV to refine molecular tools to pinpoint the vulnerable spot on the virus, scientists now can use the antibodies that attach to this spot to block the virus from infecting cells.
Led by a team from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center, scientists have discovered two naturally occurring antibodies, named VRC01 and VRC02, in an HIV-infected individual's blood. The two antibodies were detected by a center-designed molecular device to look specifically at those cells that make antibodies against HIV. The device is a modified HIV protein that is engineered to react only with antibodies specific to the site where the virus binds to infected cells. VRC01 and VRC02 block HIV infection by attaching to the CD4 binding site, which prevents the virus from latching onto immune cells.
Scientists now will use their new understanding of the structure of the precise place where VRC01 binds to HIV to design immunogens that will elicit VRC01-like antibodies when administered through a vaccine, says Gary Nabel, MD, PhD, director of the NIAID Vaccine Research Center. Nabel outlines the following possibilities in the research of VRC01 and VRC02:
- Determine whether VRC01 confers protection in macaques from a non-human primate form of HIV.
- Develop immunogens for a vaccine designed to elicit VRC01-like antibodies.
- Make preparations to study the safety and potential protective effects of VRC01 in humans.
- Develop the VRC01 antibody for other HIV prevention strategies, such a microbicides and passive immune protection.
Scientists also are generating more broadly neutralizing HIV antibodies based on structural design and are testing combinations of antibodies to protect against HIV resistance mutations, says Nabel.
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Such new developments in science can only boost HIV vaccine research. At the present time, the Seattle-based HIV Vaccine Trials Network (HVTN) lists no studies in Phase III clinical trials, says organization spokesperson Sarah Alexander. However, there are several Phase I trials, and two Phase II trials, in the field, Alexander reports.
The HVTN 505 study is using social media to engage potential study participants, says Alexander. The study is enrolling men and transwomen in Boston; New York City; Philadelphia; Washington, DC; Atlanta; Rochester, NY; Nashville, TN; Birmingham, AL; Chicago; Seattle; San Francisco; and Los Angeles. The Phase II study is looking at a prime-boost strategy of two investigational vaccines developed by scientists at NIAID's Vaccine Research Center. The two vaccines are three immunizations with recombinant DNA-based vaccine (the primer vaccine) over eight weeks followed by a single immunization with a recombinant vaccine (the boosting vaccine) based on a weakened adenovirus type 5 that carries the vaccine contents and helps stimulate the immune system.
The HVTN is running ads on Facebook that seek men who are having sex with men and who live in or near one of the cities with clinics. It also is employing a much edgier and more provocative ad, which is being placed on online gay hook-up sites to help bring in interested individuals networkwide to a web site for more information. These online ads are designed to integrate with other outreach tools such as transit ads, posters, and giveaways, including palm cards, yo-yos, and coasters.
One of the HVTN trial sites, the Fenway Health Vaccine Studies clinic in Boston, is using the popular internet site Craigslist to recruit potential study participants. By reading personal ads on Craigslist, clinic recruiters can invite individuals who appear to fit the target profile to consider participating in the trial. Such approaches use language approved by the clinic's Institutional Review Board to invite advertisers to learn more about HIV vaccine clinical trials at the clinic. These invitations include the clinic's web address for the clinic and an e-mail address to be used for response.
References
- Wu X, Yang ZY, Li Y, Hogerkorp CM, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010 Jul 8. Doi: 10.1126/science.1187659.
- Zhou T, Georgiev I, Wu X, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010 Jul 8. Doi: 10.1126/science.1192819.
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