MTBVAC: A Tuberculosis Vaccine Candidate Advancing Towards Clinical Efficacy Trials in TB Prevention

Lacámara, Sergio; Martin, Carlos

doi:10.1016/j.arbres.2023.09.009

Cited by 3 publications

(1 citation statement)

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“…It is based on the rational attenuation of M.tb with two stable and independent genetic deletions located in the phoP and fadD26 genes. It thus has a PhoP-/PDIM-deficient phenotype while maintaining the rest of the antigens present in M.tb but absent in BCG (38). Similar to BCG, vaccination with MTBVAC has been shown to induce trained innate immunity with epigenetic reprogramming of human monocytes, and it confers protection against lethal pneumonia in mice (39).…”

Section: Introductionmentioning

confidence: 99%

Low-dose M.tb infection but not BCG or MTBVAC vaccination enhances heterologous antibody titres in non-human primates

Peralta Alvarez,

Jones,

Redondo Azema

et al. 2024

Front. Immunol.

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IntroductionMycobacteria are known to exert a range of heterologous effects on the immune system. The mycobacteria-based Freund’s Complete Adjuvant is a potent non-specific stimulator of the immune response used in immunization protocols promoting antibody production, and Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccination has been linked with decreased morbidity and mortality beyond the specific protection it provides against tuberculosis (TB) in some populations and age groups. The role of heterologous antibodies in this phenomenon, if any, remains unclear and under-studied.MethodsWe set out to evaluate antibody responses to a range of unrelated pathogens following infection with Mycobacterium tuberculosis (M.tb) and vaccination with BCG or a candidate TB vaccine, MTBVAC, in non-human primates.ResultsWe demonstrate a significant increase in the titer of antibodies against SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, tetanus toxoid, and respiratory syncytial virus antigens following low-dose aerosol infection with M.tb. The magnitude of some of these responses correlated with TB disease severity. However, vaccination with BCG administered by the intradermal, intravenous or aerosol routes, or intradermal delivery of MTBVAC, did not increase antibody responses against unrelated pathogens.DiscussionOur findings suggest that it is unlikely that heterologous antibodies contribute to the non-specific effects of these vaccines. The apparent dysregulation of B cell responses associated with TB disease warrants further investigation, with potential implications for risk of B cell cancers and novel therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%