Nat Commun. 2015 Apr 10; 6(NA):6565.

PubMed ID: 25858157

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

Francica JR, Sheng Z, Zhang Z, Nishimura Y, Shingai M, Ramesh A, Keele BF, Schmidt SD, Flynn BJ, Darko S, Lynch RM, Yamamoto T, Matus-Nicodemos R, Wolinsky D; NISC Comparative Sequencing Program, Nason M, Valiante NM, Malyala P, De Gregorio E, Barnett SW, Singh M, O'Hagan DT, Koup RA, Mascola JR, Martin MA, Kepler TB, Douek DC, Shapiro L, Seder RA

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.