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

نویسندگان

  • 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
  • Betty Barnabas
  • Robert Blakesley
  • Gerry Bouffard
  • Shelise Brooks
  • Holly Coleman
  • Mila Dekhtyar
  • Michael Gregory
  • Xiaobin Guan
  • Jyoti Gupta
  • Joel Han
  • Shi-ling Ho
  • Richelle Legaspi
  • Quino Maduro
  • Cathy Masiello
  • Baishali Maskeri
  • Jenny McDowell
  • Casandra Montemayor
  • James Mullikin
  • Morgan Park
  • Nancy Riebow
  • Karen Schandler
  • Brian Schmidt
  • Christina Sison
  • Mal Stantripop
  • James Thomas
  • Pamela Thomas
  • Meg Vemulapalli
  • Alice Young
  • 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
  • Robert A. Seder
چکیده

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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015