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Vaccine2011; 30(1); 95-102; doi: 10.1016/j.vaccine.2011.10.026

Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection.

Abstract: Rhodococcus equi causes severe pneumonia in foals and has recently gained attention as a significant opportunistic pathogen in immunocompromised humans. However, no effective vaccine to prevent rhodococcosis is currently available. In this study, we have engineered the food-grade bacterium Lactococcus lactis to secrete the virulence-associated protein A from R. equi (LL-VapA). The immunogenic potential of LL-VapA strain was then evaluated after either intragastric or intranasal immunization in mice either alone or in combination with LL-Lep, a recombinant strain of L. lactis secreting biologically active leptin, a pleiotropic hormone with significant immunomodulatory properties. Intragastric administration of LL-VapA led to the highest VapA-specific mucosal response whereas intranasal administration led to the highest systemic immune responses. Cytokines released from in vitro-stimulated spleen cells show both a strong IFN-γ response and an increase of IL-4 level in all immunized groups, except for the group intranasally co-administered with both LL-VapA and LL-Lep. Strikingly, a significant reduction in R. equi viable counts in liver and spleen was observed four days after intravenous challenge with a virulent strain of R. equi in all immunized groups except for the group vaccinated by intragastric route with LL-VapA. Altogether, our results demonstrate that LL-VapA can evoke a T(H)1-based protective immune response in intranasally immunized mice. This response is enhanced when co-administered with LL-Lep strain, whereas only co-administration of LL-VapA and LL-Lep can induce a protective immune response in intragastric vaccinated mice, associated with a T(H)1/T(H)2 cytokine response.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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Publication Date: 2011-10-20 PubMed ID: 22019740DOI: 10.1016/j.vaccine.2011.10.026Google Scholar: Lookup
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  • Non-U.S. Gov't

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.

This study looks into a method of vaccination against Rhodococcus equi infection, a cause of severe pneumonia in foals and a high-risk pathogen in immunocompromised humans. The researchers have genetically modified a bacterium to secrete a protein from R. equi and found that when used as a vaccination, it led to a substantial immune response and reduction in R. equi in tested mice.

Engineering the Bacterium

  • The researchers used the bacterium Lactococcus lactis. They engineered it to secrete the virulence-associated protein A from R. equi (LL-VapA).
  • Lactococcus lactis is a food-grade bacterium, making it safe and easy to handle in a lab setting.

Testing the Vaccination

  • The engineered lactococci strain, LL-VapA, was evaluated in mice after either intragastric (through the stomach) or intranasal (through the nose) administration.
  • Testing also included administration with LL-Lep, another engineered lactococci strain that secretes biologically active leptin. Leptin is a hormone with significant immunomodulatory properties, meaning it aids in adjusting the immune response.

Results of the Vaccination

  • The results showed that intragastric administration led to the best mucosal response – mucosal immunity is an essential barrier to infection due to direct contact with the outside environment.
  • The intranasal administration resulted in the best systemic immune responses, or the generalized immune response within the body.
  • The group intranasally administered with both LL-VapA and LL-Lep, showed a marked reduction in R. equi counts in the liver and spleen after a challenge with a virulent strain of R. equi.

Conclusion

  • Overall, these findings suggest that LL-VapA can activate a T(H)1-based protective immune response in immunized mice, which can be enhanced when co-administered with the LL-Lep strain.
  • The results also indicate that the co-administration leads to protective immunity in intragastric vaccinated mice, associated with a T(H)1/T(H)2 cytokine response.
  • Though the study does not directly create a vaccine for R. equi, the results signify an important step in that direction, as well as in understanding the immune response to leptin and the benefits of co-administration in vaccines.

Cite This Article

APA
Cauchard S, Bermúdez-Humarán LG, Blugeon S, Laugier C, Langella P, Cauchard J. (2011). Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection. Vaccine, 30(1), 95-102. https://doi.org/10.1016/j.vaccine.2011.10.026

Publication

Vaccine
ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 30
Issue: 1
Pages: 95-102

Researcher Affiliations

Cauchard, S
  • Anses, Dozulé Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, 14430 Dozulé, France.
Bermúdez-Humarán, L G
    Blugeon, S
      Laugier, C
        Langella, P
          Cauchard, J

            MeSH Terms

            • Actinomycetales Infections / prevention & control
            • Adjuvants, Immunologic
            • Administration, Mucosal
            • Animals
            • Bacterial Load
            • Bacterial Proteins / genetics
            • Bacterial Proteins / immunology
            • Bacterial Vaccines / administration & dosage
            • Bacterial Vaccines / immunology
            • Cytokines / metabolism
            • Drug Carriers
            • Female
            • Lactococcus lactis / genetics
            • Leptin / genetics
            • Leptin / metabolism
            • Leukocytes, Mononuclear / immunology
            • Liver / microbiology
            • Mice
            • Mice, Inbred BALB C
            • Rhodococcus equi / immunology
            • Spleen / immunology
            • Spleen / microbiology
            • Vaccines, Synthetic / administration & dosage
            • Vaccines, Synthetic / genetics
            • Vaccines, Synthetic / immunology

            Citations

            This article has been cited 18 times.
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