title: Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.
abstract: Measurement of Ag-specific T follicular helper (TFH) cell activity in rhesus macaques has not previously been reported. Given that rhesus macaques are the animal model of choice for evaluating protective efficacy of HIV/SIV vaccine candidates and that TFH cells play a pivotal role in aiding B cell maturation, quantifying vaccine induction of HIV/SIV-specific TFH cells would greatly benefit vaccine development. In this study, we quantified SIV Env-specific IL-21-producing TFH cells for the first time, to our knowledge, in a nonhuman primate vaccine study. Macaques were primed twice mucosally with adenovirus 5 host range mutant recombinants encoding SIV Env, Rev, Gag, and Nef followed by two i.m. boosts with monomeric SIV gp120 or oligomeric SIV gp140 proteins. At 2 wk after the second protein boost, we obtained lymph node biopsy specimens and quantified the frequency of total and SIV Env-specific IL-21(+) TFH cells and total germinal center B cells, the size and number of germinal centers, and the frequency of SIV-specific Ab-secreting cells in B cell zones. Multiple correlation analyses established the importance of TFH for development of B cell responses in systemic and mucosally localized compartments, including blood, bone marrow, and rectum. Our results suggest that the SIV-specific TFH cells, initially induced by replicating adenovirus-recombinant priming, are long lived. The multiple correlations of SIV Env-specific TFH cells with systemic and mucosal SIV-specific B cell responses indicate that this cell population should be further investigated in HIV vaccine development as a novel correlate of immunity.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; guroffm@mail.nih.gov vargasinchausda@mail.nih.gov.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.affiliation: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583; and.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0002-9536-0580
authors.initials: A
authors.lastname: Demers
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Julia M
authors.initials: JM
authors.lastname: Shaw
authors.affiliation: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583; and.
authors.forename: Guobin
authors.initials: G
authors.lastname: Kang
authors.affiliation: Center for Cancer Research Core Fluorescence Imaging Facility, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Iskra
authors.initials: I
authors.lastname: Tuero
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Thomas
authors.initials: T
authors.lastname: Musich
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Venkatramanan
authors.identifier: http://orcid.org/0000-0002-8221-5982
authors.initials: V
authors.lastname: Mohanram
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.affiliation: Center for Cancer Research Core Fluorescence Imaging Facility, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Karpova
authors.affiliation: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583; and.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; guroffm@mail.nih.gov vargasinchausda@mail.nih.gov.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015686:Gene Products, env / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology*; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D015686:Gene Products, env; D018449:SAIDS Vaccines