Author: Robert T. McNally, Ph.D. Source: GenEngNews.com (
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"Turning the Tide Together" was the slogan of the 19th International AIDS Conference (AIDS 2012), the world's largest periodic gathering of HIV/AIDS researchers, held last July in Washington, D.C. The theme was an appropriate one: the tide within the HIV research community has indeed turned in recent years for the better. Let's briefly review why.
As Diane Havlir, M.D. and Chris Beyrer, M.D., recently noted in the pages of The New England Journal of Medicine, "We are at a moment of extraordinary optimism in the response to [HIV]." They go on to highlight several factors driving this optimism: a sequence of scientific advances including several trials demonstrating the partial efficacy of oral and topical chemoprophylaxis and the first signs of efficacy for an HIV vaccine candidate; evidence for the first cure of an HIV-infected person; and the result that early initiation of anti-retroviral therapy can both enhance outcomes and lower the potential for HIV transmission to sexual partners by 96%. This latter advance, write Havlir and Beyrer, "has led many to assert what had so long seemed impossible: that control of the HIV pandemic may be achievable."
Encouraging Trial Results
Indeed, significant progress is being made toward the creation of an effective vaccine. In autumn 2009, a collaborative effort between the Ministry of Health in Thailand, the U.S. Military, and the U.S. National Institute of Allergy and Infectious Disease (NIAID) announced the first encouraging results from an efficacy trial—31% prevention of infection in a 16,402-person community-based trial in Thailand. This result achieved significance in an analysis that excluded seven subjects who were found to have been infected at the time of the first vaccination, demonstrating for the first time that an HIV vaccine could prevent infection.
That trial, the third efficacy trial to be conducted for candidate HIV/AIDS vaccines, was the first to test a product designed to elicit both antibodies and T cells. This vaccine used a recombinant canarypox vaccine to prime immune responses plus protein subunits of the HIV surface protein to boost immune responses.
Additional analysis of the data suggested that protection—i.e., prevention of infection—had peaked at 60% at six months following the fourth and final vaccination, waned to 44% 12 months later, and to 34% by two years following the final vaccination—declines associated with decreasing levels of the antibody responses over time. Thus, this vaccine, if regularly boosted to maintain antibody responses, might have the potential to achieve approximately 60% prevention from infection—a credible level of protection for a new vaccine.
Until the Thai trial, many thought the best achievable outcome for an HIV/AIDS vaccine would be to induce immune responses capable of controlling, but not preventing, infection. The data from the Thai trial suggested that prevention from infection is a possibility.
With this encouraging news in the background, several companies are working toward an AIDS vaccine. Aventis-Pasteur and Global Solutions for Infectious Diseases, which supplied the vaccine for the successful Thai trial, are preparing product to test the ability of their vaccine, given with regular boosts, to protect Thai men who have sex with men. Additional efforts include those of GlaxoSmithKline, which is testing adjuvants with proteins; the Netherlands-based biopharmaceutical company Crucell, collaborating with Harvard University to develop novel adenovirus vector-based vaccines; Pennsylvania-based Inovio, which is creating a vaccine that contains viral DNA plus a cytokine; Maryland-based Profectus, which is creating DNA, protein and vesicular stomatitis virus-vectored vaccines; and Novartis, which is developing adjuvanted protein vaccines as well as viral vectors. The European company Mymetics is working on virosomes displaying gp41-derived proteins as a mucosal vaccine. Aventis-Pasteur, in collaboration with Eurovac, a European vaccine consortium, is developing additional live poxviral vectors to be used with protein boosts from Novartis.
