Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases; National Institutes of Health/National Institute of General Medical Sciences
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serologi ...
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Organizational Affiliation:
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.,Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.,Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.,Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.,Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. bjorkman@caltech.edu.,Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.,Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.,Department of Global Health, University of Washington, Seattle, WA, USA.,Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.,David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.,Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.,Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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