{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:12:56Z","timestamp":1790921576572,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"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":[[2009,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Improved vaccines capable of promoting long-term cellular immunity are urgently required for a number of diseases that remain global health problems. In the present study, we demonstrate that a tuberculosis subunit vaccine, Ag85B-ESAT-6\/CAF01 (where ESAT-6 is early secreted antigenic target of 6 kDa and CAF01 is cationic adjuvant formulation 01), induces very robust memory CD4 T cell responses that are maintained at high levels for &amp;gt;1 year postvaccination. This long-term, vaccine-induced memory response protects against a challenge with Mycobacterium tuberculosis at levels that are comparable to or better than those of bacillus Calmette-Gu\u00e9rin. Characterization of the CD4 memory T cells by multicolor flow cytometry demonstrated that the long-lived memory population consisted almost exclusively of TNF-\u03b1+IL-2+ and IFN-\u03b3+TNF-\u03b1+IL-2+ multifunctional T cells. In addition, memory cells isolated &amp;gt;1 year postvaccination maintained a strong, vaccine-specific proliferative potential. Long-term memory induced by the BCG vaccine contained fewer multifunctional T cells and was biased toward effector cells mainly of the TNF-\u03b1+IFN-\u03b3+-coexpressing subset. Ag85B-ESAT-6\/CAF01 vaccination very efficiently sustained multifunctional CD4 T cells that accumulated at the site of infection after M. tuberculosis challenge, whereas the response in unvaccinated animals was characterized by CD4 effector T cells. Our data demonstrate that adjuvanted subunit vaccines can promote long-term protective immune responses characterized by high levels of persisting multifunctional T cells and that the quality and profile of this response is sustained postinfection.<\/jats:p>","DOI":"10.4049\/jimmunol.0801592","type":"journal-article","created":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T16:48:22Z","timestamp":1244047702000},"page":"8047-8055","source":"Crossref","is-referenced-by-count":375,"title":["Tuberculosis Subunit Vaccination Provides Long-Term Protective Immunity Characterized by Multifunctional CD4 Memory T Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"Thomas","family":"Lindenstr\u00f8m","sequence":"first","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Else Marie","family":"Agger","sequence":"additional","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S","family":"Korsholm","sequence":"additional","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A","family":"Darrah","sequence":"additional","affiliation":[{"name":"Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Aagaard","sequence":"additional","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Seder","sequence":"additional","affiliation":[{"name":"Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Rosenkrands","sequence":"additional","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Andersen","sequence":"additional","affiliation":[{"name":"Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,6,15]]},"reference":[{"key":"2025032715465910200_R1","first-page":"310","article-title":"Protective \u2018immunity\u2019 by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called \u2018immunological memory.\u2019.","volume-title":"Immunol. 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