Genetic characterization of M. tuberculosis isolates from participants in a Phase 2b randomized trial evaluating the M72/AS01E tuberculosis candidate vaccine.

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dc.contributor.authorWattiau P
dc.contributor.authorOmar SV
dc.contributor.authorJoseph L
dc.contributor.authorDemoitié MA
dc.contributor.authorGilbert M
dc.contributor.authorAyles HM
dc.contributor.authorDiacon AH
dc.contributor.authorGinsberg AM
dc.contributor.authorHatherill M
dc.contributor.authorHellström E
dc.contributor.authorInnes JC
dc.contributor.authorMalahleha M
dc.contributor.authorMartinson N
dc.contributor.authorMuyoyeta M
dc.contributor.authorNduba V
dc.contributor.authorTait DR
dc.contributor.authorWilkinson RJ
dc.contributor.authorRoman F
dc.date.accessioned2026-09-09T13:46:12Z
dc.date.issued2026-Aug-28
dc.description.abstractBACKGROUND: The efficacy and safety of the M72/AS01E tuberculosis (TB) candidate vaccine were evaluated in the phase 2b randomized, placebo-controlled trial NCT01755598. In the trial, participants with Mycobacterium tuberculosis sensitization by a positive interferon-gamma release assay received either M72/AS01E or placebo (randomized 1:1) and were followed for 3 years. In this descriptive study, we genetically characterized M. tuberculosis isolates from participants who developed pulmonary TB during the trial to assess variability among isolates and evaluate the possibility of preferential progression from infection to active TB by certain strains in M72/AS01E and placebo recipients. METHODS: M. tuberculosis isolates were recovered from sputum samples and underwent DNA extraction and sequencing to assess lineage, antibiotic resistance profile, genetic variation, and genomic clusters. RESULTS: One hundred isolates (37 M72/AS01E, 63 placebo) were genetically characterized from 50 participants who developed microbiologically confirmed active pulmonary TB during the trial (20 M72/AS01E, 30 placebo). Diverse M. tuberculosis lineages were identified in both M72/AS01E and placebo recipients. No multidrug-resistant strains were detected. Genetic sequences corresponding to the antigenic components of M72/AS01E, showed low variation in pepA and high variation in PPE18. However, no apparent preferential distribution of variants was observed in M72/AS01E or placebo recipients. Cluster analyses identified 10 genomic clusters with isolates from >1 participant, illustrating complex transmission dynamics and potential of co-infection by multiple strains within individuals. CONCLUSION: This descriptive analysis showed no apparent preferential distribution of local M. tuberculosis strains in M72/AS01E or placebo recipients. These results support the continued development of this candidate vaccine.
dc.identifier.doi10.1093/infdis/jiag428
dc.identifier.urihttps://pubs.cidrz.org/handle/123456789/13682
dc.identifier.uri.pubmedhttps://pubmed.ncbi.nlm.nih.gov/42663178/
dc.relation.affiliationVaccine Clinical Laboratory and Assay Portfolio, GSK, Rixensart 1330, Belgium.
dc.relation.affiliationCentre for Tuberculosis, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg 2131, South Africa.
dc.relation.affiliationCentre for Tuberculosis, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg 2131, South Africa.
dc.relation.affiliationVaccine Clinical Laboratory and Assay Portfolio, GSK, Rixensart 1330, Belgium.
dc.relation.affiliationR&D, VxCLAP, GSK, Wavre 1300, Belgium.
dc.relation.affiliationZambart, Lusaka 10101, Zambia.
dc.relation.affiliationTASK, Cape Town 7500, South Africa.
dc.relation.affiliationClinical Development, Aeras/IAVI, New York, NY 10004, USA.
dc.relation.affiliationSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Department of Pathology, University of Cape Town, Cape Town 7925, South Africa.
dc.relation.affiliationBe Part Yoluntu Centre NPC, Mbekweni, Paarl 7626, South Africa.
dc.relation.affiliationAurum Klerksdorp CRS, The Aurum Institute, Klerksdorp 2570, South Africa.
dc.relation.affiliationDepartment of Clinical Research, Setshaba Research Centre, Soshanguve, Pretoria, 0152, South Africa.
dc.relation.affiliationPerinatal HIV Research Unit, University of the Witwatersrand, Soweto, 1864, South Africa.
dc.relation.affiliationCentre for Infectious Disease Research in Zambia (CIDRZ)
dc.relation.affiliationCentre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi 00100, Kenya.
dc.relation.affiliationClinical Development, Aeras/IAVI, Observatory, Cape Town, 7925, South Africa.
dc.relation.affiliationWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa and Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925, Republic of South Africa.
dc.relation.affiliationFrancis Crick Institute, Midland Road, London NW1 1AT, UK.
dc.relation.affiliationDepartment of Infectious Diseases, Imperial College London, W12 0NN, UK.
dc.relation.affiliationVaccine Clinical Sciences- Respiratory vaccines, GSK, Wavre 1300, Belgium.
dc.sourceThe Journal of infectious diseases
dc.titleGenetic characterization of M. tuberculosis isolates from participants in a Phase 2b randomized trial evaluating the M72/AS01E tuberculosis candidate vaccine.

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