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BMC microbiology2024; 24(1); 249; doi: 10.1186/s12866-024-03408-z

Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses.

Abstract: Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.
© 2024. The Author(s).
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Publication Date: 2024-07-08 PubMed ID: 38977999PubMed Central: PMC11229254DOI: 10.1186/s12866-024-03408-zGoogle Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study evaluated five potential vaccine candidates against Rhodococcus equi using a mouse infection model.
  • The vaccines stimulated strong immune responses and provided protection by reducing bacterial infection and tissue damage.

Background

  • Pathogen: Rhodococcus equi is a bacterium that causes serious lung and other infections, especially in foals and immunocompromised humans.
  • Current challenge: No commercial vaccines against R. equi currently exist.
  • Approach: Previously, researchers used reverse vaccinology (genome-based screening) to identify promising vaccine candidates from the entire R. equi genome.

Selected Vaccine Candidates

  • Five proteins were chosen for evaluation based on prior genome screening:
    • ABC transporter substrate-binding protein (ABC transporter)
    • Penicillin-binding protein 2 (PBD2)
    • NlpC/P60 family protein (NlpC/P60)
    • Esterase family protein (Esterase)
    • M23 family metallopeptidase (M23)

Experimental Design

  • Mouse model: BALB/c mice were immunized with each candidate vaccine.
  • Immune response assessment:
    • Measured antigen-specific T cell responses by quantifying IFN-γ and TNF-α producing CD4+ and CD8+ T cells in the spleen.
    • Evaluated Th1-type (cell-mediated) and Th2-type (humoral) immune responses and antibody production.
  • Challenge study: Mice were infected with R. equi two weeks after vaccination to assess protective efficacy.
  • Outcome measures:
    • Lung bacterial load quantification to measure infection level.
    • Histopathological examination of lung and liver tissues to assess tissue damage.
    • Evaluation of T cell memory responses indicating durability of immunity.

Results

  • All five vaccine candidates:
    • Induced significant increases in antigen-specific IFN-γ and TNF-α producing CD4+ and CD8+ T lymphocytes.
    • Produced robust Th1 and Th2 immune responses along with strong antibody generation.
    • Reduced bacterial counts in the lungs after R. equi infection compared to non-immunized controls.
    • Improved pathological outcomes by reducing lung and liver tissue damage.
    • Demonstrated potential to induce T lymphocyte memory responses, which supports long-term protection.
  • Comparative effectiveness:
    • NlpC/P60, Esterase, and M23 candidates were more effective in inducing protective immunity than ABC transporter and PBD2.

Conclusions and Implications

  • The identified antigens are promising candidates for developing vaccines to protect against R. equi infection.
  • This study expands the available R. equi antigen library, providing valuable resources for creating multivalent vaccines that target multiple proteins simultaneously.
  • The findings support further development and optimization of these vaccine candidates for potential clinical use in animals and possibly humans at risk.
  • By inducing both cell-mediated and antibody-mediated immunity, these vaccines address various aspects of immune protection needed against this intracellular pathogen.

Cite This Article

APA
Liu L, Cai P, Gu W, Duan X, Gao S, Ma X, Ma Y, Ma S, Li G, Wang X, Cai K, Wang Y, Cai T, Zhao H. (2024). Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses. BMC Microbiol, 24(1), 249. https://doi.org/10.1186/s12866-024-03408-z

Publication

BMC microbiology
ISSN: 1471-2180
NlmUniqueID: 100966981
Country: England
Language: English
Volume: 24
Issue: 1
Pages: 249
PII: 249

Researcher Affiliations

Liu, Lu
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
  • Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animal, Urumqi, China.
Cai, Peng
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Gu, Weifang
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Duan, Xingxun
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Gao, Shiwen
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Ma, Xuelian
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
  • Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animal, Urumqi, China.
Ma, Yuhui
  • Zhaosu Xiyu Horse Industry Co., Ltd., Yining, China.
Ma, Siyuan
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Li, Guoqing
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Wang, Xiangyu
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Cai, Kuojun
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Wang, Yanfeng
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Cai, Tao
  • Xinjiang Agricultural Vocational Technical College, Changji, China.
Zhao, Hongqiong
  • College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China. zhaohongqiong@sina.com.
  • Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animal, Urumqi, China. zhaohongqiong@sina.com.

MeSH Terms

  • Animals
  • Rhodococcus equi / immunology
  • Rhodococcus equi / genetics
  • Mice, Inbred BALB C
  • Mice
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / administration & dosage
  • Immunity, Humoral
  • Actinomycetales Infections / prevention & control
  • Actinomycetales Infections / immunology
  • Actinomycetales Infections / microbiology
  • Disease Models, Animal
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Immunity, Cellular
  • Female
  • Lung / microbiology
  • Lung / immunology
  • Lung / pathology
  • Bacterial Load
  • Bacterial Proteins / immunology
  • Bacterial Proteins / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism

Grant Funding

  • 2022E01027 / Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Project-Shanghai Cooperation Organization Science and Technology Partnership Program and International Science and Technology Cooperation Program
  • XJ2023G125 / Xinjiang Uygur Autonomous Region Graduate Student Innovation Program

Conflict of Interest Statement

The authors declare no competing interests.

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Citations

This article has been cited 1 times.
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