Cell Reports (Dec 2017)
Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models
- Kevin O. Saunders,
- Laurent K. Verkoczy,
- Chuancang Jiang,
- Jinsong Zhang,
- Robert Parks,
- Haiyan Chen,
- Max Housman,
- Hilary Bouton-Verville,
- Xiaoying Shen,
- Ashley M. Trama,
- Richard Scearce,
- Laura Sutherland,
- Sampa Santra,
- Amanda Newman,
- Amanda Eaton,
- Kai Xu,
- Ivelin S. Georgiev,
- M. Gordon Joyce,
- Georgia D. Tomaras,
- Mattia Bonsignori,
- Steven G. Reed,
- Andres Salazar,
- John R. Mascola,
- M. Anthony Moody,
- Derek W. Cain,
- Mireille Centlivre,
- Sandra Zurawski,
- Gerard Zurawski,
- Harold P. Erickson,
- Peter D. Kwong,
- S. Munir Alam,
- Yves Levy,
- David C. Montefiori,
- Barton F. Haynes
Affiliations
- Kevin O. Saunders
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Laurent K. Verkoczy
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Chuancang Jiang
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Jinsong Zhang
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Robert Parks
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Haiyan Chen
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Max Housman
- Department of Cell Biology, Duke University, Duke University Medical Center, Durham, NC 27710, USA
- Hilary Bouton-Verville
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Xiaoying Shen
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Ashley M. Trama
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Richard Scearce
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Laura Sutherland
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Sampa Santra
- Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- Amanda Newman
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Amanda Eaton
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Kai Xu
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20814, USA
- Ivelin S. Georgiev
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20814, USA
- M. Gordon Joyce
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20814, USA
- Georgia D. Tomaras
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Mattia Bonsignori
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Steven G. Reed
- Infectious Disease Research Institute, Seattle, WA 98102, USA
- Andres Salazar
- Oncovir, Inc., Washington, DC 20008, USA
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20814, USA
- M. Anthony Moody
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Derek W. Cain
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Mireille Centlivre
- Vaccine Research Institute (VRI), Inserm U955, Université Paris Est, AP-HP, Hôpital H. Mondor - A. Chenevier, Créteil, 94000, France
- Sandra Zurawski
- Baylor Institute for Immunology Research, Dallas, TX 75204, USA
- Gerard Zurawski
- Baylor Institute for Immunology Research, Dallas, TX 75204, USA
- Harold P. Erickson
- Department of Cell Biology, Duke University, Duke University Medical Center, Durham, NC 27710, USA
- Peter D. Kwong
- Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20814, USA
- S. Munir Alam
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Yves Levy
- Vaccine Research Institute (VRI), Inserm U955, Université Paris Est, AP-HP, Hôpital H. Mondor - A. Chenevier, Créteil, 94000, France
- David C. Montefiori
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- Barton F. Haynes
- Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.12.028
- Journal volume & issue
-
Vol. 21,
no. 13
pp. 3681 – 3690
Abstract
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.
Keywords
