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Early T follicular helper cell responses and germinal center reactions are associated with viremia control in immunized rhesus macaques

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dc.contributor.author Hait, S.H.
dc.contributor.author Vargas-Inchaustegui, D.A.
dc.contributor.author Musich, T.
dc.contributor.author Mohanram, V.
dc.contributor.author Tuero Ochoa, Iskra
dc.contributor.author Venzon, D.J.
dc.contributor.author Bear, J.
dc.contributor.author Rosati, M.
dc.contributor.author Vaccari, M.
dc.contributor.author Franchini, G.
dc.contributor.author Felber, B.K.
dc.contributor.author Pavlakis, G.N.
dc.contributor.author Robert-Guroff, M.
dc.date.accessioned 2019-07-04T16:59:31Z
dc.date.available 2019-07-04T16:59:31Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/6775
dc.description.abstract T follicular helper (T FH ) cells are fundamental in germinal center (GC) maturation and selection of antigen-specific B cells within secondary lymphoid organs. GC-resident T FH cells have been fully characterized in human immunodeficiency virus (HIV) infection. However, the role of GC T FH cells in GC B cell responses following various simian immunodeficiency virus (SIV) vaccine regimens in rhesus macaques (RMs) has not been fully investigated. We characterized GC T FH cells of RMs over the course of a mucosal/systemic vaccination regimen to elucidate GC formation and SIV humoral response generation. Animals were mucosally primed twice with replicating adenovirus type 5 host range mutant (Ad5hr)-SIV recombinants and systemically boosted with ALVAC-SIV M766 Gag/Pro/gp120-TM and SIV M766&CG7V gD-gp120 proteins formulated in alum hydroxide (ALVAC/Env) or DNA encoding SIVenv/ SIVGag/rhesus interleukin 12 (IL-12) plus SIV M766&CG7V gD-gp120 proteins formulated in alum phosphate (DNA&Env). Lymph nodes were biopsied in macaque subgroups prevaccination and at day 3, 7, or 14 after the 2nd Ad5hr-SIV prime and the 2nd vector/Env boost. Evaluations of GC T FH and GC B cell dynamics including correlation analyses supported a significant role for early GC T FH cells in providing B cell help during initial phases of GC formation. GC T FH responses at day 3 post-mucosal priming were consistent with generation of Env-specific memory B cells in GCs and elicitation of prolonged Env-specific humoral immunity in the rectal mucosa. GC Env-specific memory B cell responses elicited early post-systemic boosting correlated significantly with decreased viremia postinfection. Our results highlight the importance of early GC T FH cell responses for robust GC maturation and generation of long-lasting SIV-specific humoral responses at mucosal and systemic sites. Further investigation of GC T FH cell dynamics should facilitate development of an efficacious HIV vaccine. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartofseries Journal of Virology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject human en_US
dc.subject female en_US
dc.subject male en_US
dc.subject Article en_US
dc.subject priority journal en_US
dc.subject controlled study en_US
dc.subject Vaccine en_US
dc.subject animal experiment en_US
dc.subject animal model en_US
dc.subject animal tissue en_US
dc.subject nonhuman en_US
dc.subject virus load en_US
dc.subject animal cell en_US
dc.subject immunization en_US
dc.subject infection control en_US
dc.subject antibody specificity en_US
dc.subject immune response en_US
dc.subject correlation analysis en_US
dc.subject B lymphocyte en_US
dc.subject mucosa en_US
dc.subject rhesus monkey en_US
dc.subject simian acquired immunodeficiency syndrome en_US
dc.subject Simian immunodeficiency virus en_US
dc.subject viremia en_US
dc.subject humoral immunity en_US
dc.subject simian virus en_US
dc.subject virus envelope protein en_US
dc.subject germinal center en_US
dc.subject Germinal center en_US
dc.subject Human immunodeficiency virus vaccine en_US
dc.subject lymph node en_US
dc.subject lymphocyte function en_US
dc.subject memory cell en_US
dc.subject rectum mucosa en_US
dc.subject Rhesus macaque en_US
dc.subject T follicular helper cell en_US
dc.subject Tfh cell en_US
dc.title Early T follicular helper cell responses and germinal center reactions are associated with viremia control in immunized rhesus macaques en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/JVI.01687-18
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.02
dc.relation.issn 1098-5514

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