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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Infectious Agents and Disease

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1674831

This article is part of the Research TopicZoonotic Diseases: Epidemiology, Multi-omics, and Host-pathogen Interactions Vol IIView all 6 articles

Immunoprotective Effects of Extracellular Products of Pasteurella multocida on Mice

Provisionally accepted
Jingtao  LiJingtao Li1,2Wan  LiuWan Liu1Xiaoyu  ZhangXiaoyu Zhang1Yang  SongYang Song1Li  ChenLi Chen1Qiumei  ShiQiumei Shi1Tonglei  WuTonglei Wu1*
  • 1Hebei Normal University of Science and Technology, Qinhuangdao, China
  • 2Elanco (Sichuan) Animal Health Co., Ltd., Chengdu, China

The final, formatted version of the article will be published soon.

Background: Pasteurella multocida (P. multocida) is a globally significant pathogen causing severe infections in livestock, including hemorrhagic septicemia and respiratory diseases. Current vaccines offer limited serotype-specific protection, particularly against serotype A:3, a major cause of bovine respiratory disease. Extracellular products (ECPs) of bacteria, containing secreted proteins and enzymes, have shown promise as immunogens in other pathogens, but their potential against P. multocida remains unclear. Methods: ECPs were isolated from P. multocida serotype A:3 strain PmQA-1 and characterized via SDS-PAGE, mass spectrometry, and enzymatic activity assays. Pathogenicity was evaluated by determining the median lethal dose (LD₅₀) in mice. Mice were immunized with ECPs, formalin-killed cells (FKC), or a combination (FKC+ECPs), and immune responses (serum IgG, splenic lymphocyte proliferation, cytokine expression) were assessed over 28 days. Protective efficacy was tested via challenge with homologous (A:3) and heterologous (B:2, D:4) strains. Results: ECPs contained 157 proteins (25-100 kDa), including immunogenic factors like transferrin-binding protein A, and exhibited stable amylase activity. The LD₅₀ of ECPs in mice was 2.69 mg/mouse, inducing lesions typical of P. multocida infection. ECP-immunized mice showed peak IgG levels at day 21, enhanced lymphocyte proliferation, and upregulated TNF-α, IFN-γ, IL-1β, and IL-10 in key tissues. Challenge experiments demonstrated 100% survival against A:3 and B:2, and 90% against D:4, outperforming FKC and FKC+ECPs. Conclusion: ECPs from P. multocida serotype A:3 induce robust humoral and cellular immunity, providing broad-spectrum protection against multiple serotypes. These findings support ECPs as a promising subunit vaccine candidate for controlling P. multocida infections in livestock.

Keywords: Pasteurella multocida, Extracellular products, Vaccine, Immuneresponse, cross-protection

Received: 28 Jul 2025; Accepted: 21 Aug 2025.

Copyright: © 2025 Li, Liu, Zhang, Song, Chen, Shi and Wu. 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: Tonglei Wu, Hebei Normal University of Science and Technology, Qinhuangdao, China

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