To improve vaccines; study HIV

In the study of HIV, a set of antibodies known as bnAbs (broadly neutralizing antibodies) that recognize the HIV envelope protein have proven essential in the immune systems battle with the disease. Recently, the Duke Vaccine Institute has characterized the biochemistry that results in these bnAbs. Work has shown that early in the development of these antibodies there is a series of critical mutations at elbow antibody sites. These sites determine the ability to bind a substrate (namely HIV or not HIV in the scope of this specific research) and provide a flexibility to the binding site of the antibodies that makes them (as their name implies) able to bind to a wide variety of substrates. Of course, this would still depend on antibody specificity for a given substrate, but this is not an impossible task for an unencumbered immune system and is manageable even for some immunocompromised patients. The characterization of these mutations that allow for specific sites to actually bind HIV viral particles is an essential step in helping the immune system to fight HIV and proposes a potential target for vaccines in somehow inducing these mutations in antibody-secreting cells in a controlled fashion. Further, the site of these mutations affects specific sites of recombination associated with V, D, and J immunological segments. Given that these mutations are controlled by an imperfect recombination system, it is then scientifically reasonable to induce this type of altered recombination in order to prevent HIV infection and create a vaccine against this dangerous disease.

Moving forward, these findings published in Nature Communications suggest that research can evaluate the effect of induction of this bnAb flexibility at steps throughout the pathway of their development and secretion. This suggests that the results of this work may result in a spectrum of control over a specific aspect of the immune system, and that this work could result in both a vaccine for HIV-1 and a treatment. This could induce the formation of these antibodies prior to infection through this mutational regulation and increase the prevalence of these types of flexible bnAbs in patients who are already infected.

~Kyle Enriquez

Duke University Medical Center. (2019, February 20). New insight on potent HIV antibody could improve vaccine design: Early mutation in neutralizing antibody gives it flexibility to adapt to virus's changes. ScienceDaily. Retrieved March 1, 2019 from www.sciencedaily.com/releases/2019/02/190220174131.htm

Rory Henderson, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O. Saunders, Mattia Bonsignori, Kevin Wiehe, Barton F. Haynes, S. Munir Alam. Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-08415-7