In 2012, 1.6 million people worldwide died from AIDS-related illnesses, emphasizing the desperate need for an HIV vaccine. Now, researchers from Duke University School of Medicine in Durham, NC, say they have discovered a way to make "neutralizing" antibodies in individuals who are infected with HIV-1 - the most predominant form of the virus - paving the way for such a vaccine.
The research team, led by Dr. Barton Haynes, director of the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) and the Duke Human Vaccine Institute, recently published their findings in the journal Cell.
This latest study follows on from research conducted by the team last year. In that study, published in the journal Nature, Dr. Haynes and colleagues detailed the co-evolution of broadly neutralizing antibodies (bnAbs) and pinpointed the viruses that trigger the production of these antibodies in an HIV-infected individual.
"HIV bnAbs are potent antibodies that can protect against infection, but because they have unusual properties, they are not readily induced by current vaccines," Dr. Haynes told Medical News Today.
In this new study, the team discovered exactly how B cells - immune system cells that secrete antibodies into bodily fluids - are able to neutralize an array of HIV strains.
Neutralizing antibodies 'team up' to guide bnAbs to HIV strains
The researchers say they were surprised to find that the B cells secreted both a "helper" set of neutralizing antibodies and cross-reactive neutralizing antibodies - found in around 20% of HIV-1 infected individuals - which "teamed up" to guide a vigorous set of bnAbs to HIV strains.
They explain that these antibodies worked by targeting an outer shell region of HIV strains - known as the "viral envelopes" - to which bnAbs also stick."We have found the precise viral envelopes that arise during virus evolution in an infected individual that induce bnAbs," Dr. Haynes told us. "Moreover, the novel mechanism discovered is that two different antibody lineages cooperated to induce the antibodies."
The helper antibodies then selected the viruses that can effectively stimulate bnAbs. "That is," Dr. Haynes explained, "one antibody lineage reacted with the virus envelope and selected 'escape mutants' of viruses with virus envolpes that no longer bound to the first lineage."
"What we found was that these escape mutants, however, bound better to the bnAb lineage and therefore drove or strongly stimulated that lineage. This is the first time for demonstrating how antibodies like bnAbs develop."
He and his colleagues believe this process is repeated throughout HIV infection in order to create strong sets of antibodies that can neutralize a variety of HIV strains, and they say this discovery could pave the way for a vaccine.
Dr. Feng Gao, of the Duke Human Vaccine Institute and one of the study's first authors, says:
"The finding that the maturation of a bnAb lineage could be boosted by a helper lineage has significant implications for the development of AIDS vaccines.
Repeated immunization of immunogens derived from the initial transmitted/founder virus and escape variants with higher binding ability to a bnAb lineage may be required to induce bnAbs."
Dr. Haynes explains that the team will now conduct similar research among individuals who produce bnAbs to see whether the process discovered in this study "is a general mechanism for induction of other specificities of such antibodies."
"Then," he adds, "the ultimate proof of utility of this discovery is to use it to design immunogens that can induce broadly neutralizing antibodies by vaccination."
Using their findings, the researchers say they have already developed vaccine immunogens that selectively trigger both the helper neutralizing antibodies and cross-reactive neutralizing antibodies to produce bnAbs. These immunogens do this in a manner that simulates the natural production of bnAbs that occurs during HIV infection, according to the team.
Medical News Today recently reported on a study from Temple University School of Medicine in Philadelphia, PA, which detailed the discovery of a way to eliminate HIV permanently from cultured human cells.