Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection.
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.
Anses, Dozulé Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, 14430 Dozulé, France.
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Cauchard
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Bermúdez-Humarán
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Blugeon
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Laugier
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Langella
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Cauchard
D000193:Actinomycetales Infections / Q000517:prevention & control*; D000276:Adjuvants, Immunologic; D058956:Administration, Mucosal; D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers; D005260:Female; D013294:Lactococcus lactis / Q000235:genetics*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016929:Rhodococcus equi / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D004337:Drug Carriers; D020738:Leptin; D014614:Vaccines, Synthetic; C541879:VapA protein, Rhodococcus equi