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

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...

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Published in:Nature communications 2015-04, Vol.6 (1), p.6565, Article 6565
Main Authors: Francica, Joseph R., Sheng, Zizhang, Zhang, Zhenhai, Nishimura, Yoshiaki, Shingai, Masashi, Ramesh, Akshaya, Keele, Brandon F., Schmidt, Stephen D., Flynn, Barbara J., Darko, Sam, Lynch, Rebecca M., Yamamoto, Takuya, Matus-Nicodemos, Rodrigo, Wolinsky, David, Barnabas, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pamela, Vemulapalli, Meg, Young, Alice, Nason, Martha, Valiante, Nicholas M., Malyala, Padma, De Gregorio, Ennio, Barnett, Susan W., Singh, Manmohan, O’Hagan, Derek T., Koup, Richard A., Mascola, John R., Martin, Malcolm A., Kepler, Thomas B., Douek, Daniel C., Shapiro, Lawrence, Seder, Robert A.
Format: Article
Language:English
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Summary: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 SHIV AD8 infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV AD8 -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.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms7565