Since it was first identified as the cause of AIDS in 1983, HIV has taken more than 25 million lives. An estimated 34 million people are living with HIV, and each day an additional 7,000 become infected with the virus. Current responses to the pandemic have proved unequal to the challenge posed by HIV: For every person who begins antiretroviral treatment, two people become newly infected by the virus.
The world needs safe, effective and affordable AIDS vaccines. But making such vaccines has proved extremely difficult. HIV is the most difficult foe vaccinologists have taken on. Not only has it developed multiple mechanisms to dodge the immune response, but many different subtypes of the virus, known as clades, circulate in different regions of the world. Within those clades there is considerable variability. Researchers have not been able to design a vaccine capable of protecting people from all the variants.
Despite these challenges, researchers have in recent months made encouraging progress toward an HIV vaccine.
Proof of Concept
A clinical trial completed in Thailand in 2009 provided the first demonstration in humans that a vaccine can prevent HIV infection. Two AIDS vaccine candidates, given a few months apart in a so-called prime-boost combination, were found to be about 31% effective at preventing infection with HIV. This result, while too modest to support regulatory approval for the vaccine regimen, has generated considerable excitement within the research field.
Researchers around the world are working collaboratively to extract as much information as possible from the Thai trial data to inform future AIDS vaccine development.
Spotlight on Broadly Neutralizing Antibodies
Most licensed vaccines are thought to work by eliciting a neutralizing antibody response, which prevents a pathogen from successfully infecting cells. Many researchers expect that, to prevent HIV infection, an AIDS vaccine would need to elicit antibodies that neutralize a large number of HIV variants. Researchers have long known that such antibodies exist. Four that are widely regarded as broadly neutralizing have been extensively studied by researchers, who have long sought to isolate more such antibodies to inform HIV vaccine design efforts.
Recently, efforts to isolate new, more potent broadly neutralizing antibodies have yielded positive results. A team of researchers at and associated with IAVI, The Scripps Research Institute, Theraclone Sciences and Monogram Biosciences Inc., a LabCorp company, report in the September 2011 issue of the journal Nature the discovery a collection of 17 novel broadly neutralizing antibodies, some of which have higher potency levels than previously characterized antibodies.
These new antibodies, which reveal a number of new targets for vaccine design, were isolated by IAVI and its partners from samples collected in a continuing global search for broadly neutralizing antibodies. The effort is unprecedented in scale and distinguished by its emphasis on identifying antibodies that neutralize subtypes of HIV circulating primarily in developing countries. These findings build upon a previous discovery that yielded two potent broadly neutralizing antibodies, which were isolated by this research team in 2009 and described in the journal Science. This discovery was closely followed by the isolation of other potent and broadly neutralizing antibodies by the Vaccine Research Center (VRC) of the U.S. National Institutes of Health. Since that time, separate research teams led by the VRC and the Rockefeller University have published research regarding the isolation, characterization and mapping of antibodies found to be potent neutralizers of HIV.
Taken together, these recent results represent tremendous momentum in an area that many in the AIDS vaccine field have identified as crucial for developing a potentially powerful preventive HIV vaccine.
Replicating Successes
Many researchers are also trying to improve the quality of both the immunogens—the active part of a vaccine—used in such candidate vaccines and the genetic vehicles—or vectors—in which they are delivered. One approach aims to create vectors that are safe yet capable of replicating like any naturally occurring virus as well as many existing vaccines made from weakened viruses. Researchers have removed the replication capability from most vectors being tested in HIV vaccine trials today. Replicating vectors could provoke more effective immune responses against HIV than have so far been observed.
This idea has found a measure of support in a study on nonhuman primates.
Simian immunodeficiency virus (SIV) is closely related to HIV and causes an AIDS-like disease in non-human primates. The study of this virus provides researchers with insights into HIV infection and its prevention. In an IAVI-supported study, non-human primates were given an experimental vaccine based on a novel replicating viral vector bearing immunogens derived from SIV. When they were challenged with SIV, they went on to develop SIV infection. But, significantly, more than half of them suppressed the SIV so effectively that it could not be detected in their bloodstream.
Researchers at IAVI are currently building on these results by generating and testing several vectors that share the capacity to replicate and so mimic a natural infection.
Sustaining the Effort
As illustrated by the many scientific advances in recent years, the long-term investments that have been made in HIV vaccine development are showing distinct promise today. This hard-won momentum must be sustained. In the long run, continued progress in the field will depend on existing and novel funding mechanisms for AIDS vaccine research and development. It will also require the continued commitment and active support of governments, researchers, civil society and the communities in which the research is conducted.