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.
Publication Date: 2011-10-20 PubMed ID: 22019740DOI: 10.1016/j.vaccine.2011.10.026Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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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
Researcher Affiliations
- Anses, Dozulé Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, 14430 Dozulé, France.
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.- Lloren KKS, Senevirathne A, Lee JH. Advancing vaccine technology through the manipulation of pathogenic and commensal bacteria. Mater Today Bio 2024 Dec;29:101349.
- da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet J 2025 May;57(3):563-586.
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- Guglielmi V, Colangeli L, D'Adamo M, Sbraccia P. Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?. Int J Mol Sci 2021 Mar 20;22(6).
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- Lohmann KL, Lopez AM, Manning ST, Marques FJ, Brownlie R, Allen AL, Sangster AE, Mutwiri G, Gerdts V, Potter A, Townsend HG. Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response. Can J Vet Res 2013 Jul;77(3):161-9.
- Ma D, Gao M, Dalloul RA, Ge J, Ma C, Li J. Protective effects of oral immunization with live Lactococcus lactis expressing Eimeria tenella 3-1E protein. Parasitol Res 2013 Dec;112(12):4161-7.
- Martín R, Miquel S, Ulmer J, Kechaou N, Langella P, Bermúdez-Humarán LG. Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel disease. Microb Cell Fact 2013 Jul 23;12:71.
- White SJ, Taylor MJ, Hurt RT, Jensen MD, Poland GA. Leptin-based adjuvants: an innovative approach to improve vaccine response. Vaccine 2013 Mar 25;31(13):1666-72.
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