There’s New Hope for an HIV Vaccine

Boston University School of Medicine announced a pretty amazing discovery Monday, one that could have what the school is saying to be “significant implications for HIV vaccine development.”

Researchers at the Boston University School of Medicine (BUSM) and Duke University School of Medicine have teamed up to uncover “novel properties of special HIV antibodies.” In a new paper, published in the journal Host Cell and Microbe, the scientists describe “how some HIV antibodies experience an unusual type of mutation, a phenomenon that allows them to neutralize many different strains of HIV.”

Researchers are calling these antibodies “broadly neutralizing antibodies” or BNAbs.

According to the paper:

Antibodies develop from immune cells known as B cells. When B cells are confronted with foreign elements (known as antigens), some of them experience a high rate of mutations resulting in the substitution of an amino acid within the antibody for another. B cells whose antibodies carry variations that allow them to bind tightly with antigens proliferate, whereas those that do not die off. 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. Only a small subset of HIV-infected individuals produce BNAbs.

Scientists compared the antibody genes of HIV infected and non-infected individuals, and discovered, according to a BUSM report, that HIV infected individuals had 27 percent more insertions and 23 percent more deletions than non-infected individuals. The researchers also found that “the elevated rate of mutation persisted in all HIV-infected individuals, regardless of their ability to produce BNAbs.”

The most important part of this discovery, according to researchers, is that the “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 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.”

Since 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. They 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. According to the researchers 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 next step would be to try to create a vaccine that works by eliciting BNAbs, and this new work “suggest that strategies for such a vaccine should focus on speeding up the antibody evolution that occurs after every immunization.”