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

Rebecca M. Legere, Cristina Poveda, Jeannine A. Ott, Jocelyne M. Bray, Emma G. Villafone, Bibiana Petri da Silveira, Susanne K. Kahn, Cameron L. Martin, Chiara Mancino, Francesca Taraballi, Michael F. Criscitiello, Luc Berghman, Angela I. Bordin, Jeroen Pollet, Noah D. Cohen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 languageEnglish (US)
JournalAmerican Journal of Veterinary Research
Volume85
Issue number2
DOIs
StatePublished - 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

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