New look at widely neutralizing antibodies can improve HIV vaccine design

A new study conducted by specialists at Duke University Medical Center (USA) drew attention to the importance of studying the previously unaffected bnAb mutations that occur in the early stages and give antibodies the flexibility to adapt to changes in the structure of the HIV outer envelope protein. This flexibility allows the antibody to dock to different strains of the virus and neutralize them.

As part of exploring strategies for developing an effective vaccine against HIV, a group of microbiologists from the United States focused on the outer shell of the virus, where antibodies can be fixed and neutralize the strain.

However, according to the authors of the work, these widely neutralizing antibodies, or bnAbs, are very complex in structure of formation, which arise only under certain circumstances, which is why it is extremely difficult to track their formation and create artificial copies.

Recent observations by researchers at Duke University’s Human Vaccine Institute have highlighted the importance of studying the previously unaffected bnAb mutations that occur in the early stages and give the antibodies the flexibility to adapt to changes in the structure of the HIV outer envelope protein. This flexibility allows the antibody to dock to different strains of the virus and neutralize them.

This discovery was published in February in the journal Nature Communications.

“We focused on mutations in a specific region of the“ elbow region ”antibody, which is needed to make bnAb more flexible to perform the function to neutralize HIV-1 viruses,” said Dr. Munir Alam, director of the laboratory of the Human Vaccine Institute at Duke University.

"We found that the selection of key elbow mutations that affect flexibility is a necessary step in the early stage of maturation of widely neutralizing antibodies," the team leader explained.

Dr. Alam and his colleagues used biophysical tools and molecular dynamic modeling techniques to study changes in the molecular movement of antibodies over time. This simulation allowed them to learn about additional barriers to the development of HIV bnAb.

“Vaccine development strategies should include an indispensable requirement for selecting key elbow mutations at an early stage of immunization,” co-author Rory Henderson concluded.