The immune system is naturally capable of making antibodies against HIV, but it takes a year to reach full production.
The finding could provide a much-needed boost to HIV vaccine research, where efforts to jumpstart an effective immune response to HIV have so far met with little success.
In a paper in the Proceedings of the National Academy of Sciences, researchers at Vanderbilt University in Nashville, TN, explain how the immune system is naturally capable of making antibodies against HIV.
However, it takes a year for the body to reach full production of these “broadly neutralizing” antibodies, and less than a third of people produce them anyway.
The team decided to explore features of the antibodies that make them particularly deadly to HIV and manipulate them in order to understand what it might take for a vaccine to trigger them.
Their study was done in three phases: identification, optimization and re-engineering. First, they identified the key elements of the features (loop-like structures of amino acids), then they investigated the optimum arrangement of the loops for binding to HIV, and finally, they fused them onto a natural antibody and tested the result.
Loop-like structures bind to and disable HIV
In the identification phase, the team found that some naturally occurring antibodies have a loop-like structure that binds to HIV and disables it, and that antibodies with this feature can even be found in people who have never encountered HIV.
The loop-like structures, called long heavy-chain complementarity-determining region 3 (HCDR3), comprise 28 amino acids strung together in different combinations.
Using a molecular modeling program called Rosetta, the team identified which particular HCDR3 amino acid sequences bound most tightly to HIV.
Rosetta is a suite of computer programs for modeling large molecules. Researchers use it to study potential treatments of infectious diseases, cancers and autoimmune disorders. They also use it to develop vaccines, new enzymes and proteins.
For the optimization phase, the team then used Rosetta again, this time to find the optimum arrangement of the HCDR3 sequences that might neutralize HIV in a vaccination event.
Then, in the re-engineering phase, they fused the selected HCDR3 sequences onto PG9, a type of monoclonal antibody that is known to be a broad neutralizer of HIV. Lab tests confirmed that the re-engineered PG9 antibodies effectively neutralized HIV.
The study thus shows, with the use of computer tools, that it is possible – in principle – to neutralize HIV by boosting the effect of the HCDR3 loop-like structures in naturally occurring antibodies, even in people who have not been exposed to HIV.
The authors note that these HCDR3 loops can be found in immune B cells of people who have not been exposed to HIV, suggesting they could be a target for a structure-based vaccine that elicits a broadly neutralizing response to the virus.
One of the study leaders, James Crowe Jr., the Ann Scott Carrell Professor and director of the Vanderbilt Vaccine Center, says that a vaccine that “presents” an HIV sequence that is recognized by antibodies with the HCDR3 loops would likely increase the chance that a large proportion of those vaccinated could respond to the virus with a broad and potent antibody response.
Medical News Today recently learned how researchers are working on an implantable capsule that releases antibodies that destroy beta-amyloid – a protein thought to play a major role in the development of Alzheimer’s disease.