{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:12:23Z","timestamp":1780989143685,"version":"3.54.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4+ T follicular helper (TFH) cells. However, very little is known about the TFH response to HIV vaccination and its relative contribution to magnitude and quality of vaccine-elicited Ab titers. In this study, we investigated these questions in the context of a DNA\/modified vaccinia virus Ankara SIV vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. In addition, we determined the frequency of vaccine-induced CD4+ T cells coexpressing chemokine receptor, CXCR5 (facilitates migration to B cell follicles) in blood and whether these responses were representative of lymph node TFH responses. We show that booster modified vaccinia virus Ankara immunization induced a distinct and transient accumulation of proliferating CXCR5+ and CXCR5\u2212 CD4 T cells in blood at day 7 postimmunization, and the frequency of the former but not the latter correlated with TFH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center TFH cells, which was strongly associated with longevity, avidity, and neutralization potential of vaccine-elicited Ab response. However, CXCR3+ cells preferentially expressed the HIV coreceptor CCR5, and vaccine-induced CXCR3+CXCR5+ cells showed a moderate positive association with peak viremia following SIV251 infection. Taken together, our findings demonstrate that vaccine regimens that elicit CXCR3-biased TFH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections.<\/jats:p>","DOI":"10.4049\/jimmunol.1500083","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T12:26:16Z","timestamp":1435407976000},"page":"994-1005","source":"Crossref","is-referenced-by-count":53,"title":["Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5\u2212 CD4 T Cell Responses in Rhesus Macaques"],"prefix":"10.1093","volume":"195","author":[{"given":"Smita S","family":"Iyer","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailaja","family":"Gangadhara","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Victor","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosy","family":"Gomez","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Basu","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Joo","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Labranche","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Montefiori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Villinger","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Moss","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama Rao","family":"Amara","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703595252100_r1","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1128\/jvi.69.3.1895-1902.1995","article-title":"Bone marrow is a major site of long-term antibody production after acute viral infection","volume":"69","author":"Slifka","year":"1995","journal-title":"J. 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Immunol."},{"key":"2025030703595252100_r4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.cell.2010.10.036","article-title":"Shining a light on germinal center B cells","volume":"143","author":"Cyster","year":"2010","journal-title":"Cell"},{"key":"2025030703595252100_r5","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1182\/blood-2011-12-396648","article-title":"Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1\/09 vaccine","volume":"120","author":"Pallikkuth","year":"2012","journal-title":"Blood"},{"key":"2025030703595252100_r6","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.immuni.2013.09.007","article-title":"Circulating precursor CCR7(lo)PD-1(hi) CXCR5\u207a CD4\u207a T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure","volume":"39","author":"He","year":"2013","journal-title":"Immunity"},{"key":"2025030703595252100_r7","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5+CD4+ T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"2025030703595252100_r8","doi-asserted-by":"crossref","first-page":"176ra132","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci. 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Med."},{"key":"2025030703595252100_r17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4049\/jimmunol.173.1.68","article-title":"T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1\/Th2 effector cells that provide help for B cells","volume":"173","author":"Chtanova","year":"2004","journal-title":"J. Immunol."},{"key":"2025030703595252100_r18","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4049\/jimmunol.0903505","article-title":"Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150)","volume":"185","author":"Yusuf","year":"2010","journal-title":"J. Immunol."},{"key":"2025030703595252100_r19","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1172\/JCI63039","article-title":"CD4 T follicular helper cell dynamics during SIV infection","volume":"122","author":"Petrovas","year":"2012","journal-title":"J. Clin. 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