Despite more than 30 years of intense research, a cure or vaccine for HIV still continues to elude us. But scientists are not quitting, and slowly but surely they seem to be making promising progress in this field. For example, two new mouse studies have just come out that demonstrate that a novel vaccine candidate is able to prompt the beginnings of an immune reaction needed to prevent infection. While the results are not the “breakthrough” everyone is looking for, they are certainly a stride in the right direction.
Vaccines can be made in a variety of different ways, for example by inactivating whole pathogens or isolating particular components of them, both with the ultimate goal of stimulating a defense response from the immune system, readying it for any future assaults. But the problem with pesky HIV is that it mutates remarkably rapidly, changing its components so that they become unrecognizable by the immune system. This means that should a vaccine be successful in inducing the production of protective antibodies, they usually have such a narrow window of activity that they are effectively useless.
But there are some antibodies that are different, called broadly neutralizing antibodies (bNAbs), and scientists have high hopes that these may hold the key to producing a successful HIV vaccine. As the name suggests, rather than being specific to just one target, these antibodies are able to recognize and inhibit a range of HIV variants, or strains, and thus are much more therapeutically useful. Although a subset of HIV-positive individuals produce these antibodies, scientists have so far failed to induce their production via vaccination.
Many researchers believe the key to achieving this is by presenting the body with multiple targets, or antigens, that differ slightly, training the immune system to recognize and hone in on the more conserved elements of HIV that are found in different strains. One particular molecule that scientists are interested in is an antigen called eOD-GT8, which was engineered by researchers, headed by William Schief, at The Scripps Research Institute.
Rather than attempting to directly elicit bNAbs, this antigen is designed to stimulate the production of precursor antibodies that will eventually mature into bNAbs following prolonged exposure to the virus, The Scientist explains. So by starting off with these immature antibodies, scientists hypothesize it may be possible to encourage them to develop into bNAbs over time by gradually exposing the immune system to slightly different HIV antigens, forcing the antibodies to mutate in order to recognize more conserved regions of the virus.
When testing this molecule out in mice genetically engineered to produce antibodies similar to those found in humans, the researchers found that it was indeed able to elicit these first-line antibodies. Additionally, they found it also created a pool of antibody-producing “memory” B cells that the researchers believe could be boosted through exposure to different antigens, sort of like receiving booster shots. These findings have been reported in Science.
In another paper, published in Cell, scientists used the same molecule but a different mouse model, and once again the vaccine was able to prompt an immune response that was headed in the right direction. Unfortunately, however, the antibodies were unable to neutralize HIV. But the researchers still believe it has merit, and could be effective if combined with other molecules, which is what they will investigate next.
June 19, 2015 | Justine Alford