A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents

• Type of Material: Article
• Authors: Chelsea Carpenter, La Jolla Institute for Allergy and Immunology; John Sidney, La Jolla Institute for Allergy and Immunology; Ravi Kolla, La Jolla Institute for Allergy and Immunology; Kaustuv Nayak, International Centre for Genetic Engineering and Biotechnology; Helena Tomiyama, University of São Paulo; Claudia Tomiyama, University of São Paulo; Oscar A. Padilla, University of São Paulo; Virginie Rozot, University of Cape Town; Syed F. Ahamed, St. John’s National Academy of Sciences; Carlos Ponte, Oswaldo Cruz Foundation (FIOCRUZ); Valeria Rolla, Oswaldo Cruz Foundation (FIOCRUZ); Paulo R. Antas, Oswaldo Cruz Foundation (FIOCRUZ); Anmol Chandele, Emory University; John Kenneth, St. John’s National Academy of Sciences; Seetha Laxmi, St. John’s National Academy of Health Sciences; Edward Makgotlho, University of Cape Town; Valentina Vanini, National Institute for Infectious Diseases, Italy; Giuseppe Ippolito, National Institute for Infectious Diseases, Italy; Alexandra S. Kazanova, Central Tuberculosis Research Institute; Alexander V. Panteleev, Central Tuberculosis Research Institute; Willem Hanekom, University of Cape Town; Harriet Mayanja-Kizza, Makerere University; David Lewinsohn, Oregon Health and Science University; Mayuko Saito, Johns Hopkins University; M. Juliana McElrath, Fred Hutchinson Cancer Research Center; W. Henry Boom, Case Western Reserve University; Delia Goletti, National Institute for Infectious Diseases, Italy; Robert Gilman, Johns Hopkins University; Irina V. Lyadova, Central Tuberculosis Research Institute; Thomas J. Scriba, University of Cape Town; Esper G. Kallas, University of São Paulo; Murali Kaja, Emory University; Alessandro Sette, La Jolla Institute for Allergy and Immunology; Cecilia S. Lindestam Arlehamn, La Jolla Institute for Allergy and Immunology
• Language: English
• Date: 2015-12-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tube.2015.07.001
• Title of Journal or Parent Work: Tuberculosis
• ISSN: 1472-9792
• Volume: 95
• Issue: 6
• Start Page: 713
• End Page: 721
• Grant/Funding Information: This work was supported by the National Institutes of Health [contract HHSN272200900044C to A.S., contract HHSN266200700022C/NO1-AI-70022 to W.H.B, grant R37AI052731 to E.G.K]: the IOC/FIOCRUZ [CNPq research fellowship PQ-2-Brazil to P.R.A.]: the Italian Ministry of Health [Ricerca Corrente to D.G.], the Bill and Melinda Gates Foundation [OPP1066265 to T.J.S.], and the HIV Vaccine Trials Network [RAMP scholarship to O.A.P.].
• Keywords: Microbiology; Respiratory System; CD4; Science & Technology; Immunology; IMMUNOGENICITY; M72/AS01; PROTECTION; VACCINATED INFANTS; RESPONSES; Life Sciences & Biomedicine; INFECTION; BCG VACCINE; T cell antigen; IMMUNITY; Vaccine; Tuberculosis
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

We compared T cell recognition of 59 prevalently recognized Mycobacterium tuberculosis (MTB) antigens in individuals latently infected with MTB (LTBI), and uninfected individuals with previous BCG vaccination, from nine locations and populations with different HLA distribution, MTB exposure rates, and standards of TB care. This comparison revealed similar response magnitudes in diverse LTBI and BCG-vaccinated cohorts and significant correlation between responses in LTBIs from the USA and other locations. Many antigens were uniformly recognized, suggesting suitability for inclusion in vaccines targeting diverse populations. Several antigens were similarly immunodominant in LTBI and BCG cohorts, suggesting applicability for vaccines aimed at boosting BCG responses. The panel of MTB antigens will be valuable for characterizing MTB-specific CD4 T cell responses irrespective of ethnicity, infecting MTB strains and BCG vaccination status. Our results illustrate how a comparative analysis can provide insight into the relative immunogenicity of existing and novel vaccine candidates in LTBIs.