Antibodies in tuberculosis: functional capacity as key determinant

Infection and Immunity, vol. 94, pp. e0039425

Abstract

ABSTRACT The human immune system employs both innate and adaptive mechanisms to control pathogens, with antibodies playing a pivotal role in immune memory and defense, in particular against viral infections. In tuberculosis, antibody titers have long been used to assess immune responses, but their presence alone fails to predict protective efficacy. Recent studies highlight that antibody functionality is critical for effective immune activity. Despite widespread detection of Mycobacterium tuberculosis (Mtb)-reactive antibodies in individuals with active disease, Mtb infection, and even in healthy controls, their potential to control Mtb growth is variable and only detected in a proportion of individuals. This perspective emphasizes the need for robust functional assessment of antibodies to better understand their role in mycobacterial control and inform vaccine development. Notably, antibodies binding to purified protein derivative of Mtb , a mixture of degraded antigens from Mtb cultures, are widespread but not universally functional, underscoring the importance of Fc characteristics and epitope specificity. Initial high-throughput screening using phagocytosis and direct mycobacterial binding assays is an active indicator of antibody function. By refining and combining existing assays, as recommended in this perspective, we can better characterize antibody contributions, particularly their immunomodulatory potential, toward improved control of Mtb . Albeit antibodies may not be essential in natural protection, functional antibodies induced by vaccination may be of added value and contribute to host protection.

Authors 11

1. Krista E. van Meijgaarden Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center

2. Patricia S. Grace

   University of Pittsburgh

   Affiliation as printed

   Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine

3. Natalia Tarnovitski Freund

   Tel Aviv University

   Affiliation as printed

   Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University

4. Jacqueline M. Achkar

   Albert Einstein College of Medicine

   Affiliation as printed

   Department of Microbiology and Immunology, Albert Einstein College of Medicine

5. Thomas Lindenstrøm

   Statens Serum Institut

   Affiliation as printed

   Department of Infectious Disease Immunology, Center for Vaccine Research, Statens Serum Institut

6. Joshua Tan

   National Institutes of Health · National Institute of Allergy and Infectious Diseases

   Affiliation as printed

   Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

7. John Chan

   Rutgers, The State University of New Jersey · Rutgers New Jersey Medical School

   Affiliation as printed

   Department of Medicine, Center for Emerging Pathogens, Public Health Research Institute, New Jersey Medical School, Rutgers University

8. Carolyn G. King

   University of Basel

   Affiliation as printed

   Department of Biomedicine, Infection Immunology Laboratory, University of Basel

9. Tom H. M. Ottenhoff Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center

10. Simone A. Joosten Aachen

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center

11. on behalf of CTVD B cell group