This past summer, the Obama administration unveiled a new national strategy to curb the AIDS epidemic, a plan whose stated goals include reducing the annual number of new HIV infections by 25 percent within five years.
Motivating this crusade are a slew of sobering statistics, including an estimate from the Centers for Disease Control and Prevention that a total of 1,106,400 adults and adolescents were living with HIV infection in the US at the end of 2006. As Seth Berkley and Alan Bernstein—who are president and CEO of the International AIDS Vaccine Initiative and executive director of the Global HIV Vaccine Enterprise, respectively—wrote in The New York Times in July, “Ending HIV/AIDS urgently requires a vaccine. The evidence that a safe and effective HIV vaccine can be developed is stronger than ever.” Thus there is new hope—here we provide a review of recent developments significant to the ongoing search for a viable vaccine candidate.
One notable advance was publicized in September 2009 by the US Military HIV Research Program (MHRP) (www.hivresearch.org), which is focused on developing an effective HIV vaccine for use in Southeast Asia. In a six-year-long, community-based, Phase 3 clinical trial known as RV144, researchers demonstrated that a combination of two vaccines—based on HIV strains that commonly circulate in Thailand—was safe and modestly effective in preventing HIV infection. Specifically, the treatment consisted of a prime-boost combination of ALVAC® HIV and AIDSVAX® B/E vaccines. More than 16,000 adult volunteers in Thailand were involved in the study. Executed by the Thai Ministry of Public Health, the study included a team of leading Thai and US researchers. The trial was funded by the US government, specifically the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and the US Army Medical Research and Materiel Command, Department of Defense.
According to the trial sponsor, the US Army Surgeon General via the US Army Medical Materiel Development Activity, the results showed that the combined vaccines lowered the rate of HIV infection by 31.2 percent—a statistically significant amount—in a heterosexual population compared with placebo. For the first time ever, the ability to reduce the risk of HIV infection in humans was demonstrated. This news was presented by the lead clinical investigator on October 20, 2009 at the AIDS Vaccine 2009 symposium in Paris and subsequently published in the New England Journal of Medicine (Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009 Dec 3;361(23):2209-2220). In 2010, more than 30 US and international collaborators initiated lab studies of the patient specimens in an effort to define the immune responses mediating the vaccine-induced protection against HIV infection. These efforts are ongoing, and further work is required to develop and test a vaccine suitable for licensure and worldwide use.
In separate news from July 2010, researchers from the National Institute of Allergy and Infectious Diseases Vaccine Research Center (VRC) (www.niaid.nih.gov) reported in two Science papers (Zhou T, Georgiev I, Wu X et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 13 August 2010 329:811-817; published online 8 July 2010; Wu X, Yang Z-Y, Li Y, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 on their discovery of three human antibodies that neutralize HIV. Science 13 August 2010 329:856-861; published online 8 July 2010) on their discovery of three human antibodies that neutralize HIV. Two of these antibodies were shown to target a broad range of HIV strains. Nearly everyone infected with HIV produces some antibodies to it; the newly identified antibodies are unique in their breadth of neutralizing activity.
The VRC scientists screened blood samples from HIV-infected people around the globe for antibodies against nearly 200 strains of HIV to determine how many strains the antibodies of each patient could neutralize. Blood from one particular patient, known as “donor 45,” was found to include broadly neutralizing antibodies specific for HIV envelope proteins. The screen identified three antibody producing cells with the desired activity. Two of the cells, named VRC01 and VRC02, were found to neutralize 91 percent of the HIV strains tested, while a third, named VRC03, was found to neutralize 57 percent. This finding lends support to the principle that it is possible for the human immune system to generate broadly neutralizing antibodies. However, as noted by the authors of these Science papers, the design of a vaccine that can induce antibodies with similar specificity will require significantly more effort.
Prominent headlines aside, it is possible to get a true sense of the scope of current efforts to create an HIV vaccine by attending any one of the numerous research conferences in the field—such as those sponsored by the Global HIV Vaccine Enterprise (www.hivvaccineenterprise.org), a unique global alliance of independent organizations working together to accelerate the development of safe and effective HIV vaccines. For example, at the AIDS Vaccine 2010 Conference, which was held in Atlanta in late September, one had the option of attending close to two dozen sessions covering everything from novel immunogen delivery strategies to animal models of HIV transmission to recent advances in B-cell and protective antibody responses. Numerous smaller symposia, such as one held at the New York Academy of Sciences in May 2010, attracted speakers who addressed the challenges of developing HIV vaccines to prevent or control infection, the genetic diversity of the virus, and mechanisms that can be used to reduce HIV transmission in conjunction with a future vaccine.
According to the International AIDS Vaccine Initiative (IAVI) (www.iavi.org), funding for a preventative AIDS vaccine research topped $868 million during 2008 alone. While the investment is significant, so is the progress being made. One company seeing such progress, Atlanta-based GeoVax Labs, is testing its AIDS vaccine candidates for both preventative and therapeutic purposes. Preventative use testing is currently in a Phase 2a clinical trial, conducted by the HIV Vaccine Trials Network (HVTN) (www.hvtn.org), while patient enrollment for Phase 1 testing of its therapeutic candidate began earlier this year. GeoVax also continues its research and development efforts through funding nonclinical studies involving the use of an adjuvant with its current vaccine to further boost immune system response.
As we have briefly outlined, the search for an HIV vaccine is an ongoing research goal that continues to challenge the top minds in the infectious disease research community. Continued funding is vital, and cooperation among various agencies may play an important role.
Although it is still too early to provide a timeframe for—or quantify the probability of—ultimate success, there is a strong belief that a vaccine is a realizable goal; one that if achieved could mean a better life for millions worldwide.
About the Author
Dr. Robert McNally is the President and CEO of GeoVax Labs, Inc. (OTCBB: GOVX). GeoVax is a biotechnology company developing human vaccines for diseases caused by HIV (Human Immunodeficiency Virus – that leads to AIDS) and other infectious agents. McNally graduated with a Ph.D. in Biomedical Engineering from the University of Pennsylvania and has over 28 years of experience in academic and corporate clinical investigations, management, research, business, quality and regulatory affairs. For more information about GeoVax, please go to geovax.com.
Dr. McNally authored and submitted this article solely for the purpose of providing key expert analysis and opinion. No compensation was exchanged by either party in consideration for the publication of this material. If you're a science or medical expert willing to share your market intelligence with our readers, please contact us.
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