Co-requirement for B cells to protect against pulmonary wild-type Brucella melitensis challenge following mucosal vaccination with a live Brucella vaccine prototype
- 1Department of Infectious Diseases & Immunology, University of Florida College of Veterinary Medicine
- 2Department of Veterinary Science, College of Agriculture, Life Sciences, & Natural Resources, University of Wyoming
Abstract
Mice nasally vaccinated with the Brucella melitensis (BM) double-mutant (Δ znuA Δ norD B. melitensis -mCherry [znBM-mC]) showed increased numbers of B cells residing in the lungs 5 days post-vaccination and contributing to antigen-presentation. Studies were pursued to determine the relevance of B cells in protection conferred by mucosal znBM-mC vaccination of BALB/c compared to B cell null (µMT) mice. Two vaccination regimens were applied: oral prime, nasal boost versus a single nasal vaccination. Both methods have proven efficacious in immunocompetent mice. BALB/c mice, but not µMT mice, vaccinated with znBM-mC showed the expected efficacy. Robust T cell recruitment and differentiation were observed in the lungs in both mouse strains with no significant differences in total CD4 ⁺ and CD8 ⁺ T cells post-vaccination, although some subset phenotypic differences were noted in µMT mice. Specifically, more proinflammatory T cells were present in µMT lungs 4 weeks post-boost evident by increased numbers of TNF-α ⁺ CD4 ⁺ and CD8 ⁺ T cells, polyfunctional CD4 ⁺ and CD8 ⁺ T cells, and IFN-γ ⁺ CD8 ⁺ T cells. Examination of lung memory T cells showed no differences between vaccinated mouse groups in numbers of resident memory T cells (TRMs), central memory T cells (TCMs), and CD8 ⁺ effector memory T cells (TEMs); the CD4 ⁺ TEMs were slightly reduced in µMT lungs. Adoptive transfer of naive or immune B cells prior to wild-type (wt) BM 16M challenge in vaccinated µMT mice enabled protection. In the context of a vaccine-induced response, adoptive transfer of immune B cells into unvaccinated µMT mice failed to protect against wt BM 16M challenge demonstrating that znBM-induced protection involves both B and T cell contributions. In addition to triggering recruitment and expansion of proinflammatory and memory T cell subsets, mucosal vaccination recruits a population of B cells, which enhance protection to challenge.
Related
- Diagnostic Challenge of Crohn’s Disease in a Patient with Clinically Diagnosed Pulmonary Tuberculosis: A Case Report
- Post-Vaccination Chemosensory Dysfunction: Changes Following SARS-CoV-2 Vaccination in a Global Study.
- Optimized Epitope-Flanking Sequences Enhance Antigen Presentation and T-Cell Responses Following mRNA Vaccination.
- Distinct transcriptional states of draining lymph node T cells following influenza vaccination in individuals with underrepresented ancestries
- Recombinant GI-19 infectious bronchitis virus induction of humoral immunosuppression with reduced HI antibody response following Newcastle disease virus vaccination and bursal cell apoptosis
BibTeX
@article{goodwin2026corequirement,
title = {{Co-requirement for B cells to protect against pulmonary wild-type Brucella melitensis challenge following mucosal vaccination with a live Brucella vaccine prototype}},
author = {Zakia I. Goodwin and Carol Hoffman and Ella Bhagyaraj and David W. Pascual},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1925725},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925725/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Co-requirement for B cells to protect against pulmonary wild-type Brucella melitensis challenge following mucosal vaccination with a live Brucella vaccine prototype
AU - Zakia I. Goodwin
AU - Carol Hoffman
AU - Ella Bhagyaraj
AU - David W. Pascual
PY - 2026
DA - 2026/10/23
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1925725
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925725/full
AB - Mice nasally vaccinated with the Brucella melitensis (BM) double-mutant (Δ znuA Δ norD B. melitensis -mCherry [znBM-mC]) showed increased numbers of B cells residing in the lungs 5 days post-vaccination and contributing to antigen-presentation. Studies were pursued to determine the relevance of B cells in protection conferred by mucosal znBM-mC vaccination of BALB/c compared to B cell null (µMT) mice. Two vaccination regimens were applied: oral prime, nasal boost versus a single nasal vaccination. Both methods have proven efficacious in immunocompetent mice. BALB/c mice, but not µMT mice, vaccinated with znBM-mC showed the expected efficacy. Robust T cell recruitment and differentiation were observed in the lungs in both mouse strains with no significant differences in total CD4 ⁺ and CD8 ⁺ T cells post-vaccination, although some subset phenotypic differences were noted in µMT mice. Specifically, more proinflammatory T cells were present in µMT lungs 4 weeks post-boost evident by increased numbers of TNF-α ⁺ CD4 ⁺ and CD8 ⁺ T cells, polyfunctional CD4 ⁺ and CD8 ⁺ T cells, and IFN-γ ⁺ CD8 ⁺ T cells. Examination of lung memory T cells showed no differences between vaccinated mouse groups in numbers of resident memory T cells (TRMs), central memory T cells (TCMs), and CD8 ⁺ effector memory T cells (TEMs); the CD4 ⁺ TEMs were slightly reduced in µMT lungs. Adoptive transfer of naive or immune B cells prior to wild-type (wt) BM 16M challenge in vaccinated µMT mice enabled protection. In the context of a vaccine-induced response, adoptive transfer of immune B cells into unvaccinated µMT mice failed to protect against wt BM 16M challenge demonstrating that znBM-induced protection involves both B and T cell contributions. In addition to triggering recruitment and expansion of proinflammatory and memory T cell subsets, mucosal vaccination recruits a population of B cells, which enhance protection to challenge.
SN - 1664-3224
ER -