Publication Highlight

Could Treatment Inform Prevention? bNAB-Based Vaccines For People Living with HIV

This publication highlight is part of the SBGrid Communities Project focused on science education and demonstrating how structural biology and preclinical science connect to medicine, a collaboration between SBGrid PI Piotr Sliz and Jamaine Davis of Belmont University.

Human immunodeficiency virus (HIV) can cause a lifelong infection in exposed individuals. When HIV gets into the bloodstream, its viral capsid binds to a receptor on a human host immune cell, like CD4. CD4 cells are known as the “conductors” of the human immune system, so HIV targets the coordinated system. After attachment, the virus enters the host CD4 immune cell with proteins like integrase and reverse transcriptase that allow the HIV genetic material to be incorporated into the human genome. This technique allows for the production HIV viral material every time an infected human cell divides. Those infected CD4 cells are then targeted for destruction, decreasing the host’s immune cells, and reducing the body’s ability to fight off other infections. Due to the persistence of HIV within human cells, treatment requires a multifaceted, long-term approach. Current antiretroviral therapy (ART) is effective for disease management, but keeping up with a complex medication regimen is not always affordable, accessible, or practical for all people living with HIV (PLWH) around the world. New developments in HIV vaccines are a promising preventative and therapeutic approach for decreasing the public health burden of this virus, but conducting trials with enough individuals to draw statistically significant conclusions from the data is difficult in populations with low HIV rates.

SBGrid member Alexandra Trkola and colleagues at the University of Zurich seek to overcome this barrier by exploring the utility of vaccinating PLWH taking ART to inform the development of broadly neutralizing antibody (bNAb)-based vaccines. The strategy uses vaccines that stimulate the production of bNAbs to target HIV strains that are vulnerable to immune system attack. Since HIV undergoes viral diversification, the immune response must be equally adaptive, and a vaccine design must then enable a diversified immune cell response. Participants with diverse backgrounds who are affected by different HIV viral clades, that is a viral group with a common ancestor, should be included to provide a wide breadth of information about how the immune system may respond to the bNAb vaccine. Furthermore, vaccinating PLWH with bNAbs while carefully monitoring viral load during a period of analytic treatment interruption (ATI) could enable researchers to assess the antibody response to an increasing viral load and determine immunogens that could benefit individuals who have not been exposed to HIV. This effort could help determine antibody specificity with time to or duration of viral rebound and identify potential vaccine boosters.

Model of the VRC01 broadly neutralizing IgG antibody for HIV treatment. Courtesy Unsplash: https://unsplash.com/photos/a-purple-and-green-string-sculpture-on-a-white-surface-oc12eprOeoI

Use of ATI raises important ethical considerations about participant informed consent and the need for clear communication. Participants need to understand that vaccination is currently experimental and does not replace antiretroviral therapy. Researchers would also need to meticulously control ATI to ensure the safety of patients involved in all trials. Finally, vaccination trials including PLWH should not replace trials that include participants not exposed to HIV, but rather should occur in parallel to help generate enough data to evaluate the efficacy of HIV vaccines.

Read more in ***Journal of the International AIDS Society***.

By Mudiare Ikoba (Mudia Ikoba), Meharry Medical College

Mudiare “Mudia” Ikoba is a second-year medical student at Meharry Medical College. She completed her B.A. in Biology with a Biochemistry Concentration and a minor in Social Inequalities at Dartmouth College. When she is not studying, she enjoys being outdoors, exercising, cooking, and spending time with family and friends.