By preventing shape-shifting in a key segment of protein from HIV, the immune system can be primed to develop antibodies against the virus, which in turn could pave way for an AIDS vaccine.
Such antibodies, elicited against specific protein segments, could one day serve as the basis for a vaccine to fight many different strains of HIV or other swiftly mutating viruses.
Although a small percentage of individuals infected with HIV develop ‘broadly neutralising antibodies’ that disarm different strains of the virus, researchers have so far been unable to develop a vaccine that coaxes the immune system into making such antibodies. To get around this problem, researchers have tried to extract a key bit of protein — or epitope — that a neutralizing antibody recognizes, in the hope that the immune system will react more strongly to the epitope in isolation.
However, without the rest of the protein to hold it in place, the segment generally loses its recognizable stable structure.
Now, scientists in the United States have devised a computer model for identifying a protein that could serve as a type of scaffold, locking an epitope into the structure to which a neutralizing antibody can bind.
“We’ve figured out how to pull out those snippets, retain their structure, and teach the immune system to recognize them,” Nature quoted Peter Kwong, a structural biologist at the National Institute of Allergy, as saying. The researchers tested the approach on an epitope of gp41, a protein on the surface of HIV that helps the virus to invade and infect host cells.
The epitope is recognized by an antibody called 2F5, which can neutralize several strains of the virus. After extracting the epitope from the virus, the researchers transplanted the epitope onto a protein with a complementary structure that acted as the scaffold.
The immune systems of guinea pigs injected with this scaffold epitope complex developed antibodies very similar in structure to 2F5 antibodies.
The study has been published in Proceedings of the National Academy of Sciences.