The candidate TB vaccine, MVA85A, induces highly durable Th1 responses.
BACKGROUND
Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone.


METHODS
We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011.


RESULTS
Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA-CCR7+ central memory or CD45RA-CCR7- effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination.


CONCLUSIONS
MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Michele
M
Tameris
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Hennie
H
Geldenhuys
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Angelique KanyKany
AK
Luabeya
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Erica
E
Smit
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Jane E
JE
Hughes
Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Samantha
S
Vermaak
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Willem A
WA
Hanekom
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Mark
M
Hatherill
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Hassan
H
Mahomed
Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Helen
H
McShane
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Thomas J
TJ
Scriba
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA; D055815:Young Adult
C515370:CCR7 protein, human; D016207:Cytokines; C549320:MVA 85A; D054400:Receptors, CCR7; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens