{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:40:31Z","timestamp":1789371631316,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"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":[[2016,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA\/GM-CSF) on the immunogenicity and protection elicited by an MVA\/SIV macaque 239 vaccine. High doses of MVA\/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor \u03b14\u03b27 on plasmacytoid dendritic cells (p &amp;lt; 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p &amp;lt; 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5\u03b1 (TRIM5\u03b1) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5\u03b1-restrictive animals receiving no or the lowest dose (1 \u00d7 105 PFU) of MVA\/GM-CSF resisted all 12 challenges. In the comparable TRIM5\u03b1-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5\u03b1-restrictive animals, but not in the TRIM5\u03b1-permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA\/SIVmac239 is strongly dependent on the presence of TRIM5\u03b1 restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5\u03b1-restrictive animals, and 3) high doses of codelivered MVA\/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus-like particles.<\/jats:p>","DOI":"10.4049\/jimmunol.1600629","type":"journal-article","created":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T02:29:09Z","timestamp":1475116149000},"page":"3586-3596","source":"Crossref","is-referenced-by-count":20,"title":["High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara\/Simian Immunodeficiency Virus Vaccine Protection in TRIM5\u03b1-Restrictive Macaques"],"prefix":"10.1093","volume":"197","author":[{"given":"Sunil","family":"Kannanganat","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S","family":"Wyatt","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-628X","authenticated-orcid":false,"given":"Sailaja","family":"Gangadhara","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesarlu","family":"Chamcha","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette S","family":"Chea","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A","family":"Kozlowski","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia C","family":"LaBranche","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Chennareddi","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benton","family":"Lawson","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep B J","family":"Reddy","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany M","family":"Styles","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H","family":"Vanderford","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-6319","authenticated-orcid":false,"given":"David C","family":"Montefiori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center , Durham, NC 27705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-8564","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-3458","authenticated-orcid":false,"given":"Harriet L","family":"Robinson","sequence":"additional","affiliation":[{"name":"GeoVax, Inc. , Smyrna, GA 30080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6309-6797","authenticated-orcid":false,"given":"Rama Rao","family":"Amara","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Yerkes National Primate Research Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,11,1]]},"reference":[{"key":"2025030617574792000_r1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"2025030617574792000_r2","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1084\/jem.176.6.1693","article-title":"Generation of large numbers of dendritic cells from mouse bone marrow cultures 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