MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies.
Andrew D White, Laura Sibley, Charlotte Sarfas, Alexandra Morrison, Jennie Gullick, Simon Clark, Fergus Gleeson, Anthony McIntyre, Cecilia Lindestam Arlehamn, Alessandro Sette, Francisco J Salguero, Emma Rayner, Esteban Rodriguez, Eugenia Puentes, Dominick Laddy, Ann Williams, Mike Dennis, Carlos Martin, Sally Sharpe
Author Information
Andrew D White: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK. Andrew.white@phe.gov.uk. ORCID
Laura Sibley: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Charlotte Sarfas: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Alexandra Morrison: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Jennie Gullick: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Simon Clark: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Fergus Gleeson: The Churchill Hospital, Headington, Oxford, UK.
Anthony McIntyre: The Churchill Hospital, Headington, Oxford, UK. ORCID
Cecilia Lindestam Arlehamn: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. ORCID
Alessandro Sette: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Francisco J Salguero: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK. ORCID
Emma Rayner: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Esteban Rodriguez: Biofabri, Ponteverdra, Spain.
Eugenia Puentes: Biofabri, Ponteverdra, Spain.
Dominick Laddy: Aeras, Rockvile, MD, 20850, USA.
Ann Williams: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Mike Dennis: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
Carlos Martin: Grupo de Genética de Micobacterias, Departamento Microbiología, Universidad de Zaragoza, IIS-Aragón, CIBERES, Zaragoza, Spain. ORCID
Sally Sharpe: Public Health England, National Infection Service, Porton Down, Salisbury, SP4 0JG, UK.
A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γTNF-αIL2) and multi-(IFN-γTNF-α) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.
