A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents - 19/02/16

Doi : 10.1016/j.tube.2015.07.001

Chelsea Carpenter ^a, John Sidney ^a, Ravi Kolla ^a, Kaustuv Nayak ^b, Helena Tomiyama ^c, Claudia Tomiyama ^c, Oscar A. Padilla ^c, Virginie Rozot ^d, Syed F. Ahamed ^e, Carlos Ponte ^f, Valeria Rolla ^f, Paulo R. Antas ^f, Anmol Chandele ^b, John Kenneth ^e, Seetha Laxmi ^g, Edward Makgotlho ^d, Valentina Vanini ^h, Giuseppe Ippolito ^h, Alexandra S. Kazanova ⁱ, Alexander V. Panteleev ⁱ, Willem Hanekom ^d, Harriet Mayanja-Kizza ^j, David Lewinsohn ^k, Mayuko Saito ^l,^m,ⁿ, M. Juliana McElrath ^o, W. Henry Boom ^p, Delia Goletti ^h, Robert Gilman ^l,^m, Irina V. Lyadova ⁱ, Thomas J. Scriba ^d, Esper G. Kallas ^c, Kaja Murali-Krishna ^b,^q,^r, Alessandro Sette ^a, Cecilia S. Lindestam Arlehamn ^a,^⁎
^a La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA
^b ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India
^c Division of Clinical Immunology and Allergy, University of São Paulo Medical School, São Paulo, Brazil
^d South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa
^e Division of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Sciences, Sarjapur Road, Koramangala 2 Block, Bangaluru, Karnataka, 560034, India
^f Clinical Immunology Laboratory, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil
^g Department of Transfusion Medicine and Immunohematology, St. John's Medical College Hospital, St. John's National Academy of Health Sciences, Bangaluru, 560034, India
^h Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy
ⁱ Department of Immunology, Federal State Budgetary Scientific Institution “Central Tuberculosis Research Institute”, Moscow, Russia
^j Department of Medicine, College of Health Sciences, Faculty of Medicine, Makerere University, Kampala, Uganda
^k Oregon Health and Science University, Portland, 97239, USA
^l Johns Hopkins University, Bloomberg School of Public Health, Baltimore, 21205, USA
^m Universidad Peruana Caytano Hereida, Lima, Peru
ⁿ Department of Virology, Tohoku University, Sendai, Japan
^o Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, 98109, USA
^p Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, 44106, USA
^q Emory Vaccine Center, 1501 Clifton Road, Atlanta, GA, 30329, USA
^r Department of Pediatrics, Emory University, 1760 Haygood Drive, Atlanta, GA, 30322, USA

^∗Corresponding author. La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. Tel.: +1 858 752 6918; fax: +1 858 752 6987.

Summary

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.

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Keywords : Tuberculosis, T cell antigen, Vaccine, CD4, LTBI, BCG

Abbreviations : MTB, LTBI, BCG, TB, IGRA, TST, SFC, NTM

Plan

Ex vivo IFNγ ELISPOT assay

Factorial peptide pool testing

Results

Definition of a set of MTB antigens and clinical sites to probe T cell reactivity

Differential reactivity in the different LTBI cohorts and BCG-vaccinated MTB uninfected cohorts

Immunogenicity and immunodominance ranking of the antigen panel

Antigen selection based on uniformity of recognition

The relative ranking comparing BCG donors to LTBIs

Discussion

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Vol 95 - N° 6

P. 713-721 - décembre 2015 Retour au numéro

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A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents - 19/02/16

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