Protective efficacy of a bivalent equine influenza H3N8 virus-like particle vaccine in horses.

Equine influenza (EI) is a highly contagious acute respiratory disease of wild and domesticated horses, donkeys, mules, and other Equidae. EI is caused by the Equine Influenza virus (EIV), is endemic in many countries and outbreaks still have a severe impact on the equine industry globally. Conventional EI vaccines are widely used, but a need exists for a platform that facilitates prompt manufacturing of a highly immunogenic, antigenically matched, updated vaccine product. Here we developed a plant-produced bivalent EI virus-like particle (VLP) vaccine candidate which lacks the viral genome and are therefore non-infectious. We conducted a pilot safety/dose response study of a plant produced bivalent VLP vaccine expressing the HA proteins of Florida clade (FC) 1 and FC2 EIV in 1:1 ratio. Groups of three EIV seronegative horses were vaccinated using four antigen levels (0 sham control, 250, 500, 1000 HAU/dose component). Two doses of vaccines were administered one month apart, and horses were observed for adverse reactions, which were minimal. Sera were collected for hemagglutination inhibition (HI) testing using FC1 and FC2 viruses. One month after the second dose, all horses were challenged with the aerosolized FC1 virus. Horses were observed daily for clinical signs, and nasopharyngeal swabs were collected to quantify viral RNA using qPCR and infectious virus by titration in embryonated hens' eggs. Results showed that all vaccinated groups seroconverted prior to challenge. Post-challenge, both clinical scores and virus shedding were much reduced in all vaccinates compared to the sham-vaccinated controls. We conclude that the VLP vaccines were safe and effective in this natural host challenge model. A safe, efficacious, new-generation bivalent EI VLP vaccine produced in plants, which can promptly and regularly be antigenically matched to ensure optimal protection, will pave the way to highly competitive commercially viable vaccine products for all economic environments globally.