A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents.
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.
La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA.
Chelsea
C
Carpenter
La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA.
John
J
Sidney
La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA.
Ravi
R
Kolla
ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Kaustuv
K
Nayak
Division of Clinical Immunology and Allergy, University of São Paulo Medical School, São Paulo, Brazil.
Helena
H
Tomiyama
Division of Clinical Immunology and Allergy, University of São Paulo Medical School, São Paulo, Brazil.
Claudia
C
Tomiyama
Division of Clinical Immunology and Allergy, University of São Paulo Medical School, São Paulo, Brazil.
Oscar A
OA
Padilla
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.
Virginie
V
Rozot
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.
Syed F
SF
Ahamed
Clinical Immunology Laboratory, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil.
Carlos
C
Ponte
Clinical Immunology Laboratory, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil.
Valeria
V
Rolla
Clinical Immunology Laboratory, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil.
Paulo R
PR
Antas
ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Anmol
A
Chandele
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.
John
J
Kenneth
Department of Transfusion Medicine and Immunohematology, St. John's Medical College Hospital, St. John's National Academy of Health Sciences, Bangaluru, 560034, India.
Seetha
S
Laxmi
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.
Edward
E
Makgotlho
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy.
Valentina
V
Vanini
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy.
Giuseppe
G
Ippolito
Department of Immunology, Federal State Budgetary Scientific Institution "Central Tuberculosis Research Institute", Moscow, Russia.
Alexandra S
AS
Kazanova
Department of Immunology, Federal State Budgetary Scientific Institution "Central Tuberculosis Research Institute", Moscow, Russia.
Alexander V
AV
Panteleev
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.
Willem
W
Hanekom
Department of Medicine, College of Health Sciences, Faculty of Medicine, Makerere University, Kampala, Uganda.
Harriet
H
Mayanja-Kizza
Oregon Health and Science University, Portland, 97239, USA.
David
D
Lewinsohn
Johns Hopkins University, Bloomberg School of Public Health, Baltimore, 21205, USA; Universidad Peruana Caytano Hereida, Lima, Peru; Department of Virology, Tohoku University, Sendai, Japan.
Mayuko
M
Saito
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, 98109, USA.
M Juliana
MJ
McElrath
Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, 44106, USA.
W Henry
WH
Boom
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy.
Delia
D
Goletti
Johns Hopkins University, Bloomberg School of Public Health, Baltimore, 21205, USA; Universidad Peruana Caytano Hereida, Lima, Peru.
Robert
R
Gilman
Department of Immunology, Federal State Budgetary Scientific Institution "Central Tuberculosis Research Institute", Moscow, Russia.
Irina V
IV
Lyadova
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.
Thomas J
TJ
Scriba
Division of Clinical Immunology and Allergy, University of São Paulo Medical School, São Paulo, Brazil.
Esper G
EG
Kallas
ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India; Emory Vaccine Center, 1501 Clifton Road, Atlanta, GA, 30329, USA; Department of Pediatrics, Emory University, 1760 Haygood Drive, Atlanta, GA, 30322, USA.
Kaja
K
Murali-Krishna
La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA.
Alessandro
A
Sette
La Jolla Institute for Allergy and Immunology, Department of Vaccine Discovery, 9420 Athena Circle, La Jolla, 92037, USA. Electronic address: cecilia@lji.org.
Cecilia S
CS
Lindestam Arlehamn
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002648:Child; D005060:Europe / Q000453:epidemiology; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007194:India / Q000453:epidemiology; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013019:South Africa / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D000942:Antigens, Bacterial; D001500:BCG Vaccine
BCG; CD4; LTBI; T cell antigen; Tuberculosis; Vaccine