New Generation Equine Influenza Bivalent H3N8 VLP Vaccine

Equine influenza (EI), a World Organization for Animal Health (OIE) listed highly contagious acute respiratory disease of wild and domesticated horses, is caused by Equine Influenza virus (EIV) of the H3N8 subtype, is enzootic in many countries, and impacts the equine industry globally. The ease of transmission by direct contact and inhalation makes the spread a global concern. Antigenic drift at the hemagglutinin (HA), the prime target for neutralizing antibodies as well as the major determinant of the pathogenicity of influenza A viruses, has led to vaccine failure in various parts of the world and therefore periodic updating of vaccines is imperative. The OIE expert surveillance panel (OIE ESP) on equine influenza vaccine composition recommends a bivalent vaccine, stimulating protective immunity against the most recent H3N8 virus clades 1 and 2 of the Florida sublineages. Whilst whole-virus vaccines are still widely used and the canarypox-vectored vaccine is used in Europe, a need for an updated new generation efficacious vaccine exists. We propose to develop a plant-produced bivalent EI virus-like particle (VLP) vaccine candidate that is capable of eliciting both protective neutralizing antibodies and cell-mediated immunity. Influenza VLPs lack the viral genome and are therefore non-infectious but contain repetitive, high density display of synthetic HA viral surface proteins able to elicit robust protective immunity in horses. Our team has already succeeded in developing a highly efficacious plant-produced influenza A VLP vaccine of the H6 HA subtype for poultry resulting in significant reduction of not only viral shedding but also duration of viral shedding. Plant biopharming as an emerging manufacturing platform, recognized for its scalability, speed, versatility and low production costs is an increasingly promising molecular pharming platform for both human and veterinary vaccines. 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. Importance to the Equine Industry A highly efficacious plant-produced influenza VLP vaccine of the H6 subtype for poultry produced and validated by the team from CSIR and the University of Pretoria (South Africa) facilitated the design and production of a bivalent EI VLP vaccine candidate for horses. The team hypothesize that a safe, efficacious plant-produced, antigenically matched equine influenza hemagglutinin (HA) based virus-like particle (VLP) vaccine candidate, representing the most recent epidemiologically relevant virus strains recommended by the OIE (H3N8 Florida sublineages clade 1 and 2) will stimulate a robust humoral and cellular immune response, with antibody titers of magnitude to effectively protect horses against H3N8 EIV. Plant-produced Equine influenza (EI) VLPs will be produced, purified and the adjuvanted bivalent vaccine formulated (clade 1 and 2, ratio of 1:1) prior to a dose escalating study in horses (3 doses, 3 horses each) followed by an efficacy study. A highly efficacious antigenically matched H3N8 EIV VLP vaccine for annual or six monthly booster vaccination to confer protective immunity and curtail regional EIV outbreaks in horses globally will be advantageous. The VLP vaccine technology allows rapid antigenic updating of the EI vaccine if required. The feature of DIVA (differentiation of infected from vaccinated animals) compliance of the vaccine candidate will in addition assist in disease surveillance and outbreak management. DIVA compliance is an important goal of future vaccine development, as it facilitates disease control efforts and epidemiological investigation, but among the current generation of EIV vaccines only the canarypox-vectored vaccine has DIVA capability; this is the main reason why the canarypox-vectored vaccine was the only EIV vaccine approved for use in Australia during their 2007 outbreak. Equine influenza is already considered enzootic in the USA and much of the world. The use of live vaccines always poses a risk, not only to the animal the vaccine is administered to, but also the vaccinator. Using plant derived VLP to stimulate an efficient protective immune response is a safe alternative in theory, and if proven effective, may open up a whole new way of thinking in terms of immunity, protection and management of equine influenza globally.