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

Marco Polo Peralta Alvarez, Holly Jones, Hugo Redondo Azema, Chloe Davis, Andrew D. White, Charlotte Sarfas, Mike Dennis, Shuailin Li, Daniel Wright, Eugenia Puentes, Simon Kimuda, Sandra Belij-Rammerstorfer, Nacho Aguilo, Carlos Martin, Sally Sharpe, Helen McShane, Rachel Tanner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Introduction: Mycobacteria 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. Methods: We 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. Results: We 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. Discussion: Our 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.

Original languageEnglish
Article number1387454
JournalFrontiers in Immunology
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Peralta Alvarez, Jones, Redondo Azema, Davis, White, Sarfas, Dennis, Li, Wright, Puentes, Kimuda, Belij-Rammerstorfer, Aguilo, Martin, Sharpe, McShane and Tanner.


  • antibodies
  • BCG
  • heterologous immune responses
  • Mycobacterium tuberculosis
  • tuberculosis


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