New hope for HIV vaccine development

Scientists have found that some HIV antibodies experience an unusual type of mutation that allows them to neutralise many different strains of the virus, a finding that raises hope for an HIV vaccine.
These antibodies are called "broadly neutralising antibodies" or BNAbs and only a small subset of HIV-infected individuals produce BNAbs, researchers said.
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.

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 per cent of human antibodies contain indels; in BNAbs this figure is more than 50 per cent.

Comparing the antibody genes of HIV infected and non-infected individuals, scientists discovered that HIV infected individuals had 27 per cent more insertions and 23 per cent 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.

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 result suggests that a BNAb-eliciting vaccine is possible after all," said lead and corresponding author Thomas B Kepler, professor of microbiology at Boston University School of Medicine.
"More than 80 per cent of indels were found in genetic regions responsible for binding to the HIV virus," he added.
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 neutralising 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 neutralise HIV, only those CH31 antibodies with indels were able to accomplish the task," said Kepler.

The study was published in the journal Host Cell and Microbe.