Analysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization

Joseph R. Francica, Zizhang Sheng, Zhenhai Zhang, Yoshiaki Nishimura, Masashi Shingai, Akshaya Ramesh, Brandon F. Keele, Stephen D. Schmidt, Barbara J. Flynn, Sam Darko, Rebecca M. Lynch, Takuya Yamamoto, Rodrigo Matus-Nicodemos, David Wolinsky, Martha Nason, Nicholas M. Valiante, Padma Malyala, Ennio De Gregorio, Susan W. Barnett, Manmohan Singh, Derek T. O’Hagan, Richard A. Koup, John R. Mascola, Malcolm A. Martin, Thomas B. Kepler, Daniel C. Douek, Lawrence Shapiro and Robert A. Seder ()
Additional contact information
Joseph R. Francica: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Zizhang Sheng: Columbia University
Zhenhai Zhang: Columbia University
Yoshiaki Nishimura: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Masashi Shingai: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Akshaya Ramesh: Boston University
Brandon F. Keele: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory
Stephen D. Schmidt: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Barbara J. Flynn: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Sam Darko: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Rebecca M. Lynch: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Takuya Yamamoto: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Rodrigo Matus-Nicodemos: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
David Wolinsky: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Martha Nason: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Nicholas M. Valiante: Novartis Vaccines and Diagnostics
Padma Malyala: Novartis Vaccines and Diagnostics
Ennio De Gregorio: Novartis Vaccines and Diagnostics
Susan W. Barnett: Novartis Vaccines and Diagnostics
Manmohan Singh: Novartis Vaccines and Diagnostics
Derek T. O’Hagan: Novartis Vaccines and Diagnostics
Richard A. Koup: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John R. Mascola: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Malcolm A. Martin: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Thomas B. Kepler: Boston University
Daniel C. Douek: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lawrence Shapiro: Columbia University
Robert A. Seder: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIVAD8 infection and Env protein vaccination with eight different adjuvants. A subset of the SHIVAD8-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

Date: 2015
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DOI: 10.1038/ncomms7565

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