dc.date.accessioned | 2019-07-04T16:59:31Z | |
dc.date.available | 2019-07-04T16:59:31Z | |
dc.date.created | 2019-07-04T16:59:31Z | |
dc.date.issued | 2019 | |
dc.identifier | https://hdl.handle.net/20.500.12866/6775 | |
dc.identifier | https://doi.org/10.1128/JVI.01687-18 | |
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. | |
dc.language | eng | |
dc.publisher | American Society for Microbiology | |
dc.relation | Journal of Virology | |
dc.relation | 1098-5514 | |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.subject | human | |
dc.subject | female | |
dc.subject | male | |
dc.subject | Article | |
dc.subject | priority journal | |
dc.subject | controlled study | |
dc.subject | Vaccine | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | nonhuman | |
dc.subject | virus load | |
dc.subject | animal cell | |
dc.subject | immunization | |
dc.subject | infection control | |
dc.subject | antibody specificity | |
dc.subject | immune response | |
dc.subject | correlation analysis | |
dc.subject | B lymphocyte | |
dc.subject | mucosa | |
dc.subject | rhesus monkey | |
dc.subject | simian acquired immunodeficiency syndrome | |
dc.subject | Simian immunodeficiency virus | |
dc.subject | viremia | |
dc.subject | humoral immunity | |
dc.subject | simian virus | |
dc.subject | virus envelope protein | |
dc.subject | germinal center | |
dc.subject | Germinal center | |
dc.subject | Human immunodeficiency virus vaccine | |
dc.subject | lymph node | |
dc.subject | lymphocyte function | |
dc.subject | memory cell | |
dc.subject | rectum mucosa | |
dc.subject | Rhesus macaque | |
dc.subject | T follicular helper cell | |
dc.subject | Tfh cell | |
dc.title | Early T follicular helper cell responses and germinal center reactions are associated with viremia control in immunized rhesus macaques | |
dc.type | info:eu-repo/semantics/article | |