Identification of the Bartonella autotransporter CFA as a protective antigen and hypervariable target of neutralizing antibodies in mice

The bacterial genus Bartonella comprises numerous emerging pathogens that cause a broad spectrum of disease manifestations in humans. The targets and mechanisms of the anti-Bartonella immune defense are ill-defined and bacterial immune evasion strategies remain elusive. We found that experimentally...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-06, Vol.119 (25), p.1-11
Main Authors: Siewert, Lena K., Korotaev, Aleksandr, Sedzicki, Jaroslaw, Fromm, Katja, Pinschewer, Daniel D., Dehio, Christoph
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Bacteremia
Bacteria
Bartonella
Biological Sciences
CD40 antigen
Erythrocytes
Fc receptors
Immune system
Mass spectrometry
Mass spectroscopy
Monoclonal antibodies
Neutralizing
Protective antigen
Vaccination
Vaccine development
Vaccines
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Summary:The bacterial genus Bartonella comprises numerous emerging pathogens that cause a broad spectrum of disease manifestations in humans. The targets and mechanisms of the anti-Bartonella immune defense are ill-defined and bacterial immune evasion strategies remain elusive. We found that experimentally infected mice resolved Bartonella infection by mounting antibody responses that neutralized the bacteria, preventing their attachment to erythrocytes and suppressing bacteremia independent of complement or Fc receptors. Bartonella-neutralizing antibody responses were rapidly induced and depended on CD40 signaling but not on affinity maturation. We cloned neutralizing monoclonal antibodies (mAbs) and by mass spectrometry identified the bacterial autotransporter CFA (CAMP-like factor autotransporter) as a neutralizing antibody target. Vaccination against CFA suppressed Bartonella bacteremia, validating CFA as a protective antigen. We mapped Bartonella-neutralizing mAb binding to a domain in CFA that we found is hypervariable in both human and mouse pathogenic strains, indicating mutational antibody evasion at the Bartonella subspecies level. These insights into Bartonella immunity and immune evasion provide a conceptual framework for vaccine development, identifying important challenges in this endeavor.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2202059119