Abstract

Vaccination remains the most effective approach for preventing and controlling equine influenza virus (EIV) in horses. However, the ongoing evolution of EIV has increased the genetic and antigenic differences between currently available vaccines and circulating strains, resulting in suboptimal vaccine efficacy. As recommended by the World Organization for Animal Health (OIE), the inclusion of representative strains from clade 1 and clade 2 Florida sublineages of EIV in vaccines may maximize the protection against presently circulating viral strains. In this study, we used reverse genetics technologies to generate a bivalent EIV live-attenuated influenza vaccine (LAIV). We combined our previously described clade 1 EIV LAIV A/equine/Ohio/2003 H3N8 (Ohio/03 LAIV) with a newly generated clade 2 EIV LAIV that contains the six internal genes of Ohio/03 LAIV and the HA and NA of A/equine/Richmond/1/2007 H3N8 (Rich/07 LAIV). The safety profile, immunogenicity, and protection efficacy of this bivalent EIV LAIV was tested in the natural host, horses. Vaccination of horses with the bivalent EIV LAIV, following a prime-boost regimen, was safe and able to confer protection against challenge with clade 1 (A/equine/Kentucky/2014 H3N8) and clade 2 (A/equine/Richmond/2007) wild-type (WT) EIVs, as evidenced by a reduction of clinical signs, fever, and virus excretion. This is the first description of a bivalent LAIV for the prevention of EIV in horses that follows OIE recommendations. In addition, since our bivalent EIV LAIV is based on the use of reverse genetics approaches, our results demonstrate the feasibility of using the backbone of clade 1 Ohio/03 LAIV as a master donor virus (MDV) for the production and rapid update of LAIVs for the control and protection against other EIV strains of epidemiological relevance to horses.

Highlights

  • Equine influenza is an upper respiratory disease characterized by fever, lethargy, coughing, dyspnea, and nasal discharge that affects horses and other equids and has a severe impact on the equine industry [1]

  • During the last 10 years, the Organization for Animal Health (OIE) has recommended that commercial equine influenza virus (EIV) vaccines should include representative strains from both the clade 1 and clade 2 Florida sublineage EIVs [9]

  • A live-attenuated influenza vaccine (LAIV) for the treatment of EIV based on A/equine/Kentucky/1/1991 H3N8 has been commercially available for the treatment of EIV infections in horses but does not fulfill the OIE recommendations

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Summary

Introduction

Equine influenza is an upper respiratory disease characterized by fever, lethargy, coughing, dyspnea, and nasal discharge that affects horses and other equids and has a severe impact on the equine industry [1]. EIVs from the clade 1 Florida sublineage have caused outbreaks in other parts of the world [5,20,21,22,23,24,25] and a clade 2 EIV was detected in a horse in California that was newly imported from Europe [26]. Both clades of the Florida sublineage of EIVs are currently co-circulating and co-evolving worldwide

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