A new safe and effective cold-adapted modified live equine influenza virus vaccine that enables the differentiation of infected from vaccinated animals

An analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses (EIVs) is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted (ca) equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of the developed equine vaccine include: long-lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus at 12 months after double vaccination and the differentiation of infected from vaccinated animals. The equine influenza is an acute contagious virus disease characterized by the development of the catarrhal inflammation of the respiratory tract, general depression, short-term fever, and dry sickly cough and in the severe cases – by the development of pneumonia. Among the known equine influenza virus (EIV) subtypes H7N7 and H3N8, the latter is considered the most prevalent. These viruses pose a significant threat to equine health as well as economic problems for horse breeding [1]. At present, the most efficient way to protect horses from influenza is a complex of specific preventive measures, which are accomplished with the use of inactivated and live vaccines. Starting from 1960s, inactivated vaccines, containing the whole virus particles or their subunits, were developed and widely used in veterinary practice. The lack of virus replication, which ensures the vaccine safety, is the main advantage of this vaccine type [2]. At the same time, the main disadvantages of inactivated vaccines are weak immunogenicity caused by the formation of an exclusively humoral immune response as well as short-term immunity, which requires multiple immunizations [3, 4, 5]. For example, since the antiviral antibodies IgG(T), which are formed in the course of immunization with the inactivated vaccines, are shortlived (not more than 100 days after vaccination), triple immunization (first two with a 4 to 6 week interval and the third on the 5th or 6th month) is needed for the formation of the 12 month humoral immunity in horses [3, 4, 5]. This immunization scheme is critical because, between the second and third vaccination, horses in field conditions are the most vulnerable to influenza virus infection [7]. In addition, immunization with some of the inactivated vaccines containing adjuvants (phosphate or hydroxide of aluminum) leads to undesirable effects such as an inflammatory reaction and pain at the injection site of the intramuscularly vaccinated animals [8]. This reaction is also related to the use of chicken embryos for the vaccine production: even after the purification, the vaccine still contains significant amounts of egg proteins, which can cause undesirable reactions in the case of multiple intramuscular injections [2]. On the other hand, live attenuated vaccines unlike inactivated vaccines show the most promising results in terms of protection efficacy in horses. Among the live attenuated vaccines, the preparations produced on the basis of the cold adapted (ca) virus strains play an exceptional role. The live vaccine virus has the ability to replicate in the upper but not in the lower airways, where the temperature is elevated, unlike the wild virus, which replicates in the lower airways, that usually leads to inflammation like bronchitis and pneumonia [9]. The vaccinated horses have the light form of an influenza infection, which leads to the formation of antiviral humoral and cell immune responses. Moreover, the ca vaccine, unlike the inactivated vaccines, is capable of causing cross-reactive T-cell immunity in the vaccinated animals, which is quite important considering the high influenza virus antigenic variability (antigenic drift) [10]. The first live vaccine from the ca virus strain