The search for an HIV vaccine has taken a major step forward with the discovery of a potential Achilles heel of the virus that causes Aids.
Two powerful antibodies that attack a vulnerable spot common to many strains of HIV have been identified, improving the prospects for a vaccine against a virus that affects an estimated 33 million people and kills over 2 million each year.
The discovery is important because it highlights a potential way around HIV’s defences against the human immune system, which have so far thwarted efforts to make a workable vaccine. The hope is that a vaccine that stimulates the production of these antibodies could remain effective against HIV even as the virus mutates.
Scientists from the International Aids Vaccine Initiative (IAVI) are already examining the antibodies for clues to vaccine design. The new techniques used to discover the antibodies also promise further progress, as they should reveal other weaknesses in HIV that a vaccine might exploit.
“The findings themselves are an exciting advance toward the goal of an effective Aids vaccine because now we’ve got a new, potentially better target on HIV to focus our efforts for vaccine design,” said Wayne Koff, senior vice president of IAVI, which led the consortium behind the research.
“Having identified this one, we’re set up to find more, which should further accelerate global efforts in Aids vaccine development.”
Aids vaccine research has foundered to date because HIV mutates more quickly and easily than any other human pathogen yet discovered.
Vaccines work by teaching the immune system to recognise a particular germ and release antibodies to neutralise it, but HIV’s shape-shifting nature allows it to evade these defences very rapidly.
The newly discovered antibodies, called PG9 and PG16, are promising because they recognise parts of the virus that do not appear to change on a spike that HIV uses to infect cells. This suggests that they should be capable of attacking the virus in all its forms.
Dennis Burton, Professor of Immunology and Microbial Science at the Scripps Research Institute in La Jolla, California, who led the research team, said: “These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design.
“So now we may have a better chance of designing a vaccine that will elicit such broadly neutralising antibodies, which we think are key to successful vaccine development.”
PG9 and PG16, details of which are published in the journal Science, are particularly important because they appear to be effective against a multitude of HIV strains, including those found in Africa where Aids is most prevalent.
While a handful of similar broadly-neutralising antibodies have been identified before, these have all come from HIV patients infected with strains circulating in Europe and America.
The next challenge for the research is to identify substances called immunogens which stimulate the body’s immune system to start making the PG9 and PG16 antibodies. Such an immunogen could then be evaluated as a candidate for a vaccine.
The antibodies were discovered in a study of blood samples from more than 1,800 HIV-positive volunteers, from several countries in sub-Saharan Africa as well as the UK, the US, Thailand and Australia. The samples were then screened for broadly-neutralising antibodies against the virus, which very few patients make themselves.
The antibodies would not have been identified without a new method of hunting for them, developed by a company called Monogram Biosciences. Christos Petropoulos, its chief scientific officer, said: “If you think of it as a fishing expedition, we and the rest of the field were previously using the wrong bait in the search for HIV-specific broadly neutralizing antibodies.”
Seth Berkley, president and chief executive of IAVI, said: “The story of the discovery of these two new antibodies demonstrates the challenges of Aids vaccine research but also the power of the collaboration that formed to produce this advance.
“This is what can happen when you have researchers from the global North and South, from academia and industry, from within and outside the HIV field, working together in a framework to speed innovation. By working in this manner, I am confident we will continue to move toward solving the AIDS vaccine challenge, one of the greatest scientific and public health challenges of our time.”
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