title: Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sundling
authors.forename: Mattias N E
authors.initials: MN
authors.lastname: Forsell
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Bimal
authors.initials: B
authors.lastname: Chakrabarti
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008253:Macaca mulatta; D011485:Protein Binding; D012995:Solubility; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D054299:env Gene Products, Human Immunodeficiency Virus