title: Independent expansion of epitope-specific plasma cell responses upon HIV-1 envelope glycoprotein immunization.
abstract: Abs that bind the functional envelope glycoprotein (Env) spike are considered critical for a broadly effective prophylactic HIV-1 vaccine. The difficulty in eliciting such Abs by vaccination is partially attributed to the immunodominance of hydrophilic, surface-exposed variable protein regions of Env. However, little is known about the potential for competition between B cells that recognize distinct and distal epitopes on Env during protein subunit vaccination. In this study, we address this basic question at the level of Ab-secreting cells and serum IgG using a pair of isogenic soluble Env trimers, designated wildtype and gV3, which differ only in their potential to activate B cell responses against the highly immunogenic V3 region of Env. Immunization of mice with gV3 resulted in a markedly lower Ag-specific response compared with that induced by wildtype Env and could be explained by a loss of V3-directed reactivities. There was no redistribution of the response to other regions of Env in gV3-inoculated mice, suggesting that the epitope-specific Ab-secreting cell responses measured after boost are independently regulated rather than dictated by direct or indirect competition between B cells recognizing different structural elements of Env. This information is relevant for ongoing efforts in Env immunogen design to focus responses on conserved neutralizing determinants and for our general understanding of B cell responses to large-protein Ags that display numerous B cell epitopes.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden. mattias.forsell@ki.se
authors.forename: Mattias N E
authors.initials: MN
authors.lastname: Forsell
authors.forename: Martina
authors.initials: M
authors.lastname: Soldemo
authors.forename: Pia
authors.initials: P
authors.lastname: Dosenovic
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D021122:Protein Subunits / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D021122:Protein Subunits; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1