Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Abstract

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.

• Authors: Amelia Escolano, Harry B Gristick, Morgan E Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y Oliveira, Joy Pai, Anthony P West Jr, Christopher O Barnes, Alexander A Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V Voll, David C Montefiori, Michael S Seaman, Anna Gazumyan, Murillo Silva, Andrew T McGuire, Leonidas Stamatatos, Darrell J Irvine, Lance Wells, Malcolm A Martin, Pamela J Bjorkman, Michel C Nussenzweig
• Journal: Nature (Nature) Vol. 570 Issue 7762 Pg. 468-473 (06 2019) ISSN: 1476-4687 [Electronic] England
• PMID: 31142836 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• Antibodies, Neutralizing
• Antigen-Antibody Complex
• HIV Antibodies
• Immunodominant Epitopes
• Polysaccharides

Topics

• AIDS Vaccines (immunology)
• Amino Acid Sequence
• Animals
• Antibodies, Neutralizing (chemistry, genetics, immunology, ultrastructure)
• Antibody Affinity
• Antibody Specificity (immunology)
• Antigen-Antibody Complex (immunology)
• B-Lymphocytes (cytology, immunology)
• Cell Proliferation
• Clone Cells (cytology, immunology)
• Cloning, Molecular
• Cross-Priming (immunology)
• Cryoelectron Microscopy
• Female
• HIV Antibodies (chemistry, genetics, immunology, ultrastructure)
• HIV-1 (chemistry, immunology)
• Immunodominant Epitopes (chemistry, immunology, ultrastructure)
• Lymphocyte Activation
• Macaca mulatta (immunology)
• Male
• Mice
• Models, Molecular
• Polysaccharides (immunology)
• Rabbits
• Somatic Hypermutation, Immunoglobulin
• Vaccination