HIV Vaccine One Step Closer to Reality

The war on HIV, that tricky little guy has avoided every thing we could throw at it in a broad sense. Sure a few people here and there get lucky, but we have yet to actually make any sort of we’re going to kick your ass headway [don’t worry it’s the technical term for it]. That is hopefully going to change with a new scientific discovery that has enormous implications for HIV vaccine development. Researchers have uncovered novel properties of special HIV antibodies that promise to help eliminate HIV.

Researchers have determined how some HIV antibodies experience an unusual type of mutation, a phenomenon that allows them to neutralize many different strains of HIV. These antibodies are called “broadly neutralizing antibodies,” or since we shorten everything in science to acronyms BNAbs.

First a little background for those of you who aren’t familiar with the immune system, antibodies develop from immune cells known as B cells. When those B cells are confronted with foreign elements [also known as antigens], some of them experience a high rate of mutations this results in the substitution of an amino acid within the antibody for another. This is not your typical “bad form” of mutation that causes problems like cancer in the body, namely because B cells whose antibodies carry variations that allow them to bind tightly with antigens proliferate, whereas those that do not die off. Making mutation advantageous in this [and many other] instance.

Thus, the immune system is able to adapt constantly by utilizing its own very fast version of evolution. More rarely, the antibodies will experience more dramatic changes than single amino acid substitutions. When whole strings of amino acids are inserted or deleted, this is known as an indel. Less than four percent of human antibodies contain indels; in BNAbs this figure is more than 50 percent. This new antibody type was hard to find because only a small subset of HIV-infected individuals produce BNAbs.

Comparing the antibody genes of HIV infected and non-infected individuals, scientists surprisingly discovered that HIV infected individuals had 27 percent more insertions and 23 percent more deletions than non-infected individuals. They also found this elevated rate of mutation persisted in all HIV-infected individuals, regardless of their ability to produce BNAbs, this might not be too shocking since the HIV virus itself mutates at a rapid pace.

However, and most importantly, this high rate of indels was due to an overall increase in mutation frequency rather than something special associated with HIV itself, or unusual characteristics of the people who are able to make BNAbs. This is important because this means that the discovery does not apply to just a small subset of people.

“This result suggests that a BNAb-eliciting vaccine is possible after all,” explained lead and corresponding author Thomas B. Kepler, PhD, professor of microbiology at BUSM. “More than 80 percent of indels were found in genetic regions responsible for binding to the HIV virus,” he added.

Because the BNAb indels don’t result from special characteristics of the people who make them, the researchers suspected that the indels may be important for the antibody function. The team studied one particular BNAb called CH31, which has a very large indel, to see what role these indels might have played in the acquisition of broad neutralizing activity. They found that the indel was the key event in the development of CH31.

As the team found out, just putting the indel into antibodies that did not originally have it, increased its effectiveness eight-fold; taking it away from ones that did have it initially, made them much worse.

“When tested on their ability to broadly neutralize HIV, only those CH31 antibodies with indels were able to accomplish the task,” said Kepler.

The researchers say that the more we understand about the unusual pathway the BNAbs take to develop, the better chance we will have in inducing them. This new study unravels a particularly complex BNAb pathway.

The great hope in the quest to prevent HIV-1 is the development of a single vaccine that can cover multiple forms of HIV-1. A vaccine that works by eliciting BNAbs is a major goal, and this new work suggest that strategies for such a vaccine should focus on speeding up the antibody evolution that occurs after every immunization. This new finding suggests that such a strategy could work in everyone, not just a lucky few.

So when should we expect to see this vaccine hitting shelves? Well it might be awhile, the US in particular has some of the toughest standards for approval from the FDA. This means that even if/when the research is completed we might be looking at another 3-5 years before it gets added into the normal rounds of vaccines children get. But for anyone living a semi-normal life with HIV/AIDS right now, which thanks to medical advancements is mostly possible, this is probably the news they were hoping for.

Although HIV/AIDS is no longer the death sentence it was just a few short years back, it is still a life sentence, which can be just as bad. So here’s to hoping that we get that vaccine soon.

Want to get in on the forefront of this understanding? You probably want the full study, which can be found —here!

Sources: 
Verkoczy L. & Barton F. Haynes (2014). HIV-1 Envelope gp41 Broadly Neutralizing Antibodies: Hurdles for Vaccine Development, PLoS Pathogens, 10 (5) e1004073. DOI: http://dx.doi.org/10.1371/journal.ppat.1004073