Intramuscular but not nebulized administration of a mRNA vaccine against Rhodococcus equi stimulated humoral immune responses in neonatal foals.
Abstract: Design and evaluate immune responses of neonatal foals to a mRNA vaccine expressing the virulence-associated protein A (VapA) of Rhodococcus equi. Methods: 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. Conclusions: Further evaluation of the immunogenicity and efficacy of IM mRNA encoding VapA in foals is warranted.
Publication Date: 2023-12-11 PubMed ID: 38056076DOI: 10.2460/ajvr.23.09.0208Google Scholar: Lookup
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- Journal Article
Summary
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This study was about designing and evaluating an mRNA vaccine for neonatal foals to tackle the Rhodococcus equi bacteria. It was found that administering this vaccine through an intramuscular injection was effective in inducing an immune response, but administering it through a nebulizer was not.
Research Design
- The researchers wanted to test a mRNA vaccine that expresses the virulence-associated protein A (VapA) of the bacteria Rhodococcus equi.
- To do this, they created a few different mRNA constructs encoding VapA and tested their expression level using equine bronchial cells. The construct with the highest expression was selected for immunization.
- The selected vaccine was then provided to groups of 30 healthy Quarter Horse foals at two points in time (when they were 2 and 21 days old).
- The foals were divided into 5 groups, each treated with a different method: nebulization at two dosages, intramuscular injection at one dosage, intramuscular injection with VapA protein (as positive control), or nebulized water (as negative control).
Results and Key Findings
- The nebulized mRNA wasn’t immunogenic i.e., it did not trigger an immune response.
- Foals immunized intramuscularly with VapA mRNA showed a significant increase in anti-VapA IgG4/7 activity.
- The propensity of foals with anti-VapA IgG1 activity depended significantly on the method of immunization i.e., post intramuscular administration the anti-VapA IgG1 activity was greater.
- Natural exposure to virulent Rhodococcus equi caused an immune response in some of the foals in the negative control group.
Conclusions and Further Steps
- The authors propose that more research is needed to ascertain the immunogenicity and efficacy of intramuscularly administered mRNA encoding VapA in foals.
Cite This Article
APA
Legere RM, Poveda C, Ott JA, Bray JM, Villafone EG, Silveira BPD, Kahn SK, Martin CL, Mancino C, Taraballi F, Criscitiello MF, Berghman L, Bordin AI, Pollet J, Cohen ND.
(2023).
Intramuscular but not nebulized administration of a mRNA vaccine against Rhodococcus equi stimulated humoral immune responses in neonatal foals.
Am J Vet Res, 85(2).
https://doi.org/10.2460/ajvr.23.09.0208 Publication
Researcher Affiliations
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX.
- Texas Children's Hospital Center for Vaccine Development, Houston, TX.
- Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, 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.
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX.
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX.
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX.
- Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX.
- Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- 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.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
- Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX.
- Texas Children's Hospital Center for Vaccine Development, Houston, TX.
- Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
MeSH Terms
- Animals
- Horses
- Animals, Newborn
- Immunity, Humoral
- mRNA Vaccines
- Bacterial Proteins / genetics
- Rhodococcus equi / genetics
- Leukocytes, Mononuclear
- Immunoglobulin G
- RNA, Messenger / genetics
- Actinomycetales Infections / prevention & control
- Actinomycetales Infections / veterinary
- Horse Diseases / prevention & control
- Virulence Factors / genetics
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