Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates

Christopher Sundling, Mattias N.E. Forsell, Sijy O'Dell, Yu Feng, Bimal Chakrabarti, Srinivas S. Rao, Karin Loré, John R. Mascola, Richard T. Wyatt, Iyadh Douagi, Gunilla B. Karlsson Hedestam

Research output: Contribution to journalArticle

Abstract

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoproteins (Envs) have proven difficult to elicit by immunization. Therefore, to identify effective Env neutralization targets, efforts are underway to define the specificities of bNAbs in chronically infected individuals. For a prophylactic vaccine, it is equally important to define the immunogenic properties of the heavily glycosylated Env in healthy primates devoid of confounding HIV-induced pathogenic factors. We used rhesus macaques to investigate the magnitude and kinetics of B cell responses stimulated by Env trimers in adjuvant. Robust Env-specific memory B cell responses and high titers of circulating antibodies developed after trimer inoculation. Subsequent immunizations resulted in significant expansion of Env-specific IgG-producing plasma cell populations and circulating Abs that displayed increasing avidity and neutralization capacity. The neutralizing activity elicited with the regimen used was, in most aspects, superior to that elicited by a regimen based on monomeric Env immunization in humans. Despite the potency and breadth of the trimer-elicited response, protection against heterologous rectal simian-HIV (SHIV) challenge was modest, illustrating the challenge of eliciting sufficient titers of cross-reactive protective NAbs in mucosal sites. These data provide important information for the design and evaluation of vaccines aimed at stimulating protective HIV-1 immune responses in humans.

Original languageEnglish (US)
Pages (from-to)2003-2017
Number of pages15
JournalJournal of Experimental Medicine
Volume207
Issue number9
DOIs
StatePublished - Aug 30 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sundling, C., Forsell, M. N. E., O'Dell, S., Feng, Y., Chakrabarti, B., Rao, S. S., Loré, K., Mascola, J. R., Wyatt, R. T., Douagi, I., & Karlsson Hedestam, G. B. (2010). Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates. Journal of Experimental Medicine, 207(9), 2003-2017. https://doi.org/10.1084/jem.20100025