Abstract
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.
Original language | English (US) |
---|---|
Journal | American Journal of Veterinary Research |
Volume | 85 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2024 |
Keywords
- foal
- immunity
- mRNA
- Rhodococcus equi
- vaccine
- Animals, Newborn
- Actinomycetales Infections/prevention & control
- Immunoglobulin G
- Leukocytes, Mononuclear
- Virulence Factors/genetics
- mRNA Vaccines
- RNA, Messenger/genetics
- Animals
- Bacterial Proteins/genetics
- Immunity, Humoral
- Horses
- Rhodococcus equi/genetics
- Horse Diseases/prevention & control
ASJC Scopus subject areas
- General Veterinary