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BRIEF RESEARCH REPORT article

Front. Immunol.

Sec. Microbial Immunology

The natural human adaptive IgG-specific immune response is skewed towards nonprotective tail domains of DNABII proteins

Provisionally accepted
Kathryn Q. WilbanksKathryn Q. Wilbanks1Jaime D. RhodesJaime D. Rhodes1Steven D GoodmanSteven D Goodman1,2Sanjay SethiSanjay Sethi3Timothy MurphyTimothy Murphy3Lauren O BakaletzLauren O Bakaletz1,2*
  • 1Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, United States
  • 2The Ohio State University, Columbus, United States
  • 3University at Buffalo, Buffalo, United States

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Biofilm-mediated infections are highly recalcitrant to antibiotics and host immune system clearance. The matrix that envelopes biofilm-resident bacteria is stabilized by extracellular DNA as well as integrated ubiquitous bacterial DNABII proteins that exhibit potential as a common therapeutic target. We've shown that a monoclonal antibody directed against the immunoprotective DNA-binding 'tips' of DNABII proteins disrupts diverse biofilms, prevents their formation, and augments disease resolution in four distinct pre-clinical models. As an immunogen, a synthetic peptide that mimics the immunoprotective domains induces a response with equivalent effectiveness. Confoundingly, however, sera from both children with chronic otitis media (OM) and healthy adults preferentially recognize non-protective 'tail' domains of DNABII proteins. Thus, we wondered if this is a universal, natural immune response that contributes to biofilm recalcitrance. Here, we used both surface plasmon resonance and ELISA assays to assess sera from 16 healthy children, 16 additional children with chronic OM, 15 adults with chronic obstructive pulmonary disease, and 30 people with cystic fibrosis for relative recognition of synthetic peptides that mimicked either the protective or the non-protective DNABII protein domains. In 74 of 77 sera assessed (96%), we found significant IgG-specific preferential immune recognition of non-protective domains. These new data support continued development of our DNABII-directed vaccine candidate designed to re-direct the immune response toward the protective domains to mediate biofilm eradication.

Keywords: Active immunization, Bacterial Pathogenesis, Biofilm, Hu, IHF, immune redirection, originalantigenic sin

Received: 28 Aug 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Wilbanks, Rhodes, Goodman, Sethi, Murphy and Bakaletz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lauren O Bakaletz

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material