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Pathogenicity and vaccine protection of circulating pertactin- and filamentous hemagglutinin-deficient Bordetella pertussis strains
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DOI：10.1080/22221751.2026.2640283.png)
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Abstract
En 中文
The increasing emergence of vaccine antigen-deficient Bordetella pertussis (Bp) variants has raised concerns regarding disease control and prevention. Here, we characterized the pathogenicity and vaccine protection of circulating pertactin-deficient (PRN−), filamentous hemagglutinin-deficient (FHA−), and double-deficient (FHA−PRN−) Bp isolates. In vitro assays assessed bacterial proliferation, autoaggregation, adhesion to and invasion of A549 cells, associated cytokine responses in THP-1 cells, and cell death induction in both A549 and THP-1 cells. In vivo, the lung colonization, pulmonary immune responses, and the protection of three pertussis-containing vaccines against antigen-deficient isolates were investigated in a murine model. The PRN– isolate exhibited WT-like proliferation, adhesion, invasion, and lung colonization, and induced markedly enhanced pro-inflammatory responses and increased A549 cell death. The FHA− and FHA−PRN− isolates showed faster in vitro growth, reduced autoaggregation, adhesion, invasion, and THP-1 cell death levels, similar lung colonization, alongside a slight increase in inflammatory cytokine induction compared with the WT strain. Flow cytometric analysis revealed that the PRN− isolate induced a WT-like lung immune cell profile, whereas the FHA− and FHA−PRN− isolates induced a higher proportion of neutrophils, and FHA− infection was associated with reduced alveolar macrophage and dendritic cells. DTcP and DTaP vaccines provided distinct levels of protection against antigen-deficient isolates. Breakthrough infections were observed in 69.57% (16/23) vaccinated mice challenged with the FHA−PRN− strain. In conclusion, PRN and FHA deficiencies could alter some pertussis virulence-associated phenotypes and modulate host immune responses, thereby contributing to changes in vaccine protection.
Keywords:
Bordetella pertussis
pertactin deficiency
filamentous hemagglutinin deficiency
pathogenicity
vaccine protection
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