NIAID-Funded HIV Vaccine Research Generates Key Antibodies in Animal Models

A trio of studies being published today in the journals Science and Cell describes advances toward the development of an HIV vaccine. The three study teams all demonstrated techniques for stimulating animal cells to produce antibodies that either could stop HIV from infecting human cells in the laboratory or had the potential to evolve into such antibodies. Each of the research teams received funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

In one study, published in Science, researchers demonstrate that a laboratory-designed molecular complex can stimulate rabbits and monkeys to produce powerful neutralizing antibodies against a tough-to-neutralize HIV strain. The complex is similar to the part of HIV that binds to cells--a structure that has been difficult to copy as the kind of stand-alone molecule that an HIV vaccine potentially would need. This study was jointly led by John P. Moore, PhD, of Weill Medical College of Cornell University, and Roger W. Sanders, PhD, of the Academic Medical Center, Amsterdam, and the Weill Medical College.

In another study, published in Cell, scientists took the first step toward confirming the prevailing hypothesis of how an HIV vaccine will need to be designed to elicit antibodies that stop a wide range of HIV strains from infecting human cells. The researchers demonstrated in genetically modified mice that an HIV vaccine regimen likely would need to expose the immune system to one type of protein to elicit a nascent antibody with the potential to be broadly neutralizing, and then present another type of protein later on to coax a more mature form of the antibody toward final development. This study was led by Michel C. Nussenzweig, MD, PhD, of the Howard Hughes Medical Institute at The Rockefeller Universiy, and William R. Schief, PhD, of the Scripps Research Institute.

In the third study, published in Science, researchers used an engineered protein to stimulate B cells in genetically modified mice to produce antibodies that are precursors of the NIAID-discovered VRC01 antibody, which can neutralize a wide range of HIV strains. This study provides strong evidence that the engineered protein can kick off the production of VRC01-class broadly neutralizing antibodies in the scientists' mouse model by targeting VRC01-class progenitor cells and has potential to do the same in humans. The research was led by David Nemazee, PhD, William R. Schief, PhD, and Dennis R. Burton of the Scripps Research Institute.

Together, the three papers represent an important starting point for developing HIV vaccines that can elicit broadly neutralizing antibodies in people.

References:

P Dosenovic et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell DOI: 10.1016/j.cell.2015.06.003 (2015).

JG Jardine et al. Priming a broadly neutralizing antibody response to HIV using a germline-targeting immunogen. Science DOI: 10.1126/science.aac5894 (2015).

RW Sanders et al. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science DOI: 10.1126/science.aac4223 (2015).

Source: NIH/National Institute of Allergy and Infectious Diseases

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