{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:18:23Z","timestamp":1793085503272,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009342","name":"Aeras","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009342","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Global tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium tuberculosis (M.tb).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and M.tb-uninfected adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 98 healthy, HIV-uninfected, bacillus Calmette-Gu\u00e9rin\u2013vaccinated, South African adults. M.tb infection was defined by QuantiFERON-TB (QFT) assay. QFT-negative participants received two vaccinations of different concentrations of H56 in 500 nmol of IC31 to enable dose selection for further vaccine development. Subsequently, QFT-positive and QFT-negative participants were randomized to receive two or three vaccinations to compare potential schedules. Participants were followed for safety and immunogenicity for 292 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>H56:IC31 showed acceptable reactogenicity profiles irrespective of dose, number of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse events were observed. The three H56 concentrations tested induced equivalent frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was only immunogenic in QFT-negative participants who received three vaccinations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Two or three H56:IC31 vaccinations at the lowest dose induced durable antigen-specific CD4 T-cell responses with acceptable safety and tolerability profiles in M.tb-infected and M.tb-uninfected adults. Additional studies should validate applicability of vaccine doses and regimens to both QFT-positive and QFT-negative individuals.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT01865487).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201802-0366oc","type":"journal-article","created":{"date-parts":[[2018,8,9]],"date-time":"2018-08-09T17:30:30Z","timestamp":1533835830000},"page":"220-231","source":"Crossref","is-referenced-by-count":105,"title":["Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-576X","authenticated-orcid":false,"given":"Sara","family":"Suliman","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and"},{"name":"Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-2836","authenticated-orcid":false,"given":"Angelique Kany Kany","family":"Luabeya","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and"},{"name":"Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South 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T.","family":"Hoff","sequence":"additional","affiliation":[{"name":"Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongkai","family":"Shi","sequence":"additional","affiliation":[{"name":"Aeras, Rockville, Maryland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dereck","family":"Tait","sequence":"additional","affiliation":[{"name":"Aeras, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Kromann","sequence":"additional","affiliation":[{"name":"Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Ruhwald","sequence":"additional","affiliation":[{"name":"Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn Tucker","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Aeras, Rockville, Maryland; 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