Intramuscular but not nebulized administration of a mRNA vaccine against Rhodococcus equi stimulated humoral immune responses in neonatal foals.

Autor:	Legere RM; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Poveda C; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX.; Texas Children's Hospital Center for Vaccine Development, Houston, TX., Ott JA; Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Bray JM; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Villafone EG; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Silveira BPD; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Kahn SK; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Martin CL; Department of Poultry Science, College of Agriculture & Life Sciences, Texas A&M University, College Station, TX., Mancino C; Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX.; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX., Taraballi F; Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX.; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX., Criscitiello MF; Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Berghman L; Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.; Department of Poultry Science, College of Agriculture & Life Sciences, Texas A&M University, College Station, TX., Bordin AI; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX., Pollet J; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX.; Texas Children's Hospital Center for Vaccine Development, Houston, TX., Cohen ND; Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
Jazyk:	angličtina
Zdroj:	American journal of veterinary research [Am J Vet Res] 2023 Dec 11; Vol. 85 (2). Date of Electronic Publication: 2023 Dec 11 (Print Publication: 2024).
DOI:	10.2460/ajvr.23.09.0208
Abstrakt:	Objective: Design and evaluate immune responses of neonatal foals to a mRNA vaccine expressing the virulence-associated protein A (VapA) of Rhodococcus equi. Animals: Cultured primary equine respiratory tract cells; Serum, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from 30 healthy Quarter Horse foals. Methods: VapA expression was evaluated by western immunoblot in cultured equine bronchial cells transfected with 4 mRNA constructs encoding VapA. The mRNA construct with greatest expression was used to immunize foals at ages 2 and 21 days in 5 groups: (1) 300 μg nebulized mRNA (n = 6); (2) 600 μg nebulized mRNA (n = 4); (3) 300 μg mRNA administered intramuscularly (IM) (n = 5); (4) 300 μg VapA IM (positive controls; n = 6); or (5) nebulized water (negative controls; n = 6). Serum, BALF, and PBMCs were collected at ages 3, 22, and 35 days and tested for relative anti-VapA IgG1, IgG4/7, and IgA activities using ELISA and cell-mediated immunity by ELISpot. Results: As formulated, nebulized mRNA was not immunogenic. However, a significant increase in anti-VapA IgG4/7 activity (P < .05) was noted exclusively in foals immunized IM with VapA mRNA by age 35 days. The proportion of foals with anti-VapA IgG1 activity > 30% of positive control differed significantly (P = .0441) between negative controls (50%; 3/6), IM mRNA foals (100%; 5/5), and IM VapA (100%; 6/6) groups. Natural exposure to virulent R equi was immunogenic in some negative control foals. Clinical Relevance: Further evaluation of the immunogenicity and efficacy of IM mRNA encoding VapA in foals is warranted.
Databáze:	MEDLINE
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