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.
Abstract: We evaluated the immunogenic and protective potential of a recombinant VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular injection on days 1 and 15 of the study; control foals (n = 7) received a phosphate-buffered saline (PBS) solution. All foals were challenged by intrabronchial administration of 5 × 10⁶ R. equi 103⁺ on day 29. Bronchoalveolar lavages were done on days 15, 29, and 36 and total cell count, differential cell count, rVapA-stimulated cell proliferation and interferon (IFN)-γ mRNA expression determined. Clinical examination, complete blood (cell) counts, serology for VapA-specific antibodies, and culture of nasal and fecal swabs were done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50 and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a significant increase in VapA-specific immunoglobulin (Ig) production, with total IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-γ mRNA by BAL cells was increased in the vaccinated foals following challenge. Postmortem lung severity scores did not differ between groups. Two foals shed virulent R. equi in feces; however, real-time polymerase chain reaction (PCR) revealed the isolates to be different from the challenge strain. Nous avons évalué le potentiel immunogène et protecteur d’un vaccin recombinant VapA/oligodéoxynucléotide CpG (ODN) 2395 chez des poulains nouveau-nés soumis à une infection défi par Rhodococcus equi. Les poulains (n = 8) étaient vaccinés par voie intramusculaire aux jours 1 et 15 de l’étude; les poulains témoins (n = 7) ont reçu une injection d’une solution de saline tamponnée (PBS). Tous les poulains ont été challengés par administration intra-bronchique de 5 × 106R. equi 103+ au jour 29. Des lavages broncho-alvéolaires (LBA) ont été effectués aux jours 15, 29 et 36 et on détermina le nombre total de cellules, un dénombrement cellulaire différentiel, la prolifération des cellules rVapA stimulées et l’expression d’ARNm de l’interféron (IFN)-γ. Un examen clinique, des comptages cellulaires sanguins complets, une analyse sérologique pour détecter les anticorps spécifiques contre VapA, et une culture d’écouvillons nasal et fécal ont été effectués aux jours 1, 15, 29, 36, 43 et 50. Les poulains ont été euthanasiés au jour 50 et la sévérité de la pneumonie notée sur une échelle de 4 points. La vaccination a causé une augmentation significative de la production d’immunoglobulines (Ig) spécifiquement dirigées contre VapA, les quantités totales d’IgG et d’IgG(T) ayant augmentées au jour 15. L’expression d’ARNm de l’IFN-γ spécifique au VapA par les cellules des LBA était augmentée chez les poulains vaccinés suite au challenge. Aucune différence ne fut notée dans les pointages de sévérité des lésions pulmonaires lors des examens post-mortem. Deux poulains excrétaient du R. equi virulent dans leurs fèces; toutefois, l’analyse par réaction d’amplification en chaîne par la polymérase (PCR) a démontré que ces isolats étaient différents de la souche utilisée pour le challenge.(Traduit par Docteur Serge Messier).
Publication Date: 2013-10-09 PubMed ID: 24101791PubMed Central: PMC3700440
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research tested the efficacy of a new VapA/CpG oligodeoxynucleotide (ODN) 2395 vaccine in protecting foals from Rhodococcus equi pneumonia. Despite boosting VapA-specific antibodies and interferon-γ in the subjects, the vaccine failed to prevent the disease.
Experimental Design
- The study involved a total of 15 foals, which were divided into two different groups – one receiving the new vaccine (8 foals), and the other functioning as a control and receiving a phosphate-buffered saline solution (7 foals).
- All foals were then exposed to Rhodococcus equi bacteria through an intrabronchial delivery on the 29th day of the study.
- Foals were evaluated through regular bronchoalveolar lavages, blood cell counts, clinical examinations, serological analysis, and fecal and nasal swab cultures conducted on specific days of the study.
- Foals were humanely euthanized on day 50 of the study, with their lung tissue examined and scored for pneumonia severity.
Results
- Vaccinated foals displayed a significant increase in VapA-specific immunoglobulin (IgG and IgGT) production by day 15, indicating a successful immunogenic response to the vaccine.
- The expression of VapA-specific interferon-γ mRNA in bronchoalveolar lavage cells increased following the Rhodococcus equi challenge in vaccinated foals, also suggesting an initiated immune response to the bacteria.
- However, there was no observable difference between the lung severity scores of vaccinated and control foals, indicating a failure of the vaccine to protect against Rhodococcus equi pneumonia.
- Interestingly, two of the foals shed virulent Rhodococcus equi in their feces, but these strains were different from the original challenge strain, as determined through polymerase chain reaction (PCR) analysis.
Implications
- The study reveals that the tested VapA/CpG ODN 2395 vaccine, despite triggering an immune response in neonatal foals, fails to protect them against Rhodococcus equi pneumonia.
- Delving deeper into the immune response post-vaccination and understanding the reasons for failure of protection remains crucial.
- This study emphasizes the ongoing need to explore more effective vaccination strategies to protect neonatal foals from this serious disease.
Cite This Article
APA
Lohmann KL, Lopez AM, Manning ST, Marques FJ, Brownlie R, Allen AL, Sangster AE, Mutwiri G, Gerdts V, Potter A, Townsend HG.
(2013).
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, 77(3), 161-169.
Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan (Lohmann, Manning, Marques, Sangster, Townsend); Vaccine & Infectious Disease Organization (VIDO)-International Vaccine Centre (Inter-Vac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan (Lopez, Brownlie, Mutwiri, Gerdts, Potter, Townsend); Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan (Allen).
MeSH Terms
- Actinomycetales Infections / immunology
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / prevention & control
- Actinomycetales Infections / veterinary
- Animals
- Animals, Newborn
- Bacterial Proteins / genetics
- Bacterial Proteins / immunology
- Bacterial Vaccines / genetics
- Bacterial Vaccines / immunology
- Bacterial Vaccines / standards
- Bronchoalveolar Lavage Fluid / cytology
- Bronchoalveolar Lavage Fluid / immunology
- Horse Diseases / immunology
- Horse Diseases / microbiology
- Horse Diseases / prevention & control
- Horses
- Interferon-gamma / genetics
- Interferon-gamma / immunology
- Linear Models
- Male
- Oligodeoxyribonucleotides / genetics
- Oligodeoxyribonucleotides / immunology
- Pneumonia / immunology
- Pneumonia / microbiology
- Pneumonia / prevention & control
- Pneumonia / veterinary
- RNA, Messenger / chemistry
- RNA, Messenger / genetics
- Random Allocation
- Real-Time Polymerase Chain Reaction / veterinary
- Rhodococcus equi / genetics
- Rhodococcus equi / immunology
- Vaccination / standards
- Vaccination / veterinary
- Vaccines, Synthetic / genetics
- Vaccines, Synthetic / immunology
- Vaccines, Synthetic / standards
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