{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:43:24Z","timestamp":1783997004143,"version":"3.55.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the European Union\u2019s Seventh Framework Programme for research, technological development and demonstration","award":["602843"],"award-info":[{"award-number":["602843"]}]},{"name":"The German Center for Infection Research DZIF CRG","award":["80207STRUK (TTU.03.703)"],"award-info":[{"award-number":["80207STRUK (TTU.03.703)"]}]},{"DOI":"10.13039\/501100005040","name":"Bontius Stichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005040","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stichting Tabernaleporis"},{"name":"Leiden University Medical Center Strategic Fund for Leiden Controlled Human Infection Center"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30\u03bcg (n = 8) or 100\u03bcg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4<jats:sup>+<\/jats:sup> T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4<jats:sup>+<\/jats:sup> T cells were CD161<jats:sup>+<\/jats:sup> memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1.<\/jats:p>\n<jats:p>In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4<jats:sup>+<\/jats:sup> T cell responses that correlate with specific antibody levels. As these CD4<jats:sup>+<\/jats:sup> T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009732","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T18:44:47Z","timestamp":1633113887000},"page":"e0009732","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5827-419X","authenticated-orcid":true,"given":"Yoanne 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