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

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

Resumen: 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.

Idioma: Inglés

DOI: 10.3389/fimmu.2024.1387454

Año: 2024

Publicado en: Frontiers in Immunology 15 (2024), [12 pp.]
ISSN: 1664-3224

Factor impacto JCR: 5.9 (2024)

Categ. JCR: IMMUNOLOGY rank: 32 / 183 = 0.175 (2024) - Q1 - T1

Factor impacto SCIMAGO: 1.941 - Immunology and Allergy (Q1) - Immunology (Q1)

Tipo y forma: Article (Published version)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)