Texas Equine Veterinary Association

www.teva-online.org • Page 20 Equine influenza or flu is a common r e s p i r a t o r y infection of horses. Typical clinical signs include fever, nasal discharge, and a persistent, harsh, dry cough. Other clinical signs may include lethargy, depression, and decreased feed intake. Horses usually recover clinically from uncomplicated influenza within two weeks if they are rested, but coughing may persist. Secondary bacterial infections can be common and may prolong the recovery period. Dispersal of horses after horse shows, sales, race meetings and other events where equine influenza virus has been circulating may lead to widespread dissemination of the virus to the wider equine population. 3 Influenza viruses were first isolated in the 1930s and vaccines were used in humans beginning in the 1940s, with vaccines becoming available for use in horses 20 years later. The existence of a reservoir of virus in aquatic birds and the highly variable nature of the influenza virus makes worldwide eradication unlikely. 3,4 Equine influenza has two surface proteins, haemagglutinin (HA) and neuraminidase (NA). Haemagglutinin has an essential role in binding of EIV virus to the host (equine) cell surface and entry of virus into the cell; whereas NA is involved in virus release from the invaded host (equine) cell. 3,5 Both HA and NA create an immune response, inducing antibody response in the infected or vaccinated animal. Antigenic drift involves the accumulation (over time) of amino acid changes in the surface proteins, HA and NA. Randomly occurring mutations subtly change the HA so that, over time, the HA becomes more and more unrecognizable by the antibodies (circulating in the horse) created to an earlier virus strain. 3 Cross-reacting antibodies have been shown to be much less efficient at neutralizing (killing) virus infectively than strain-specific (direct) antibody. 10 If enough changes occur in the HA, the virus may escape neutralization (killing) altogether by the antibody. Research suggests that only one or two amino acid changes (antigenic drift) in HA can lead to a significant difference in antigenicity between strains. 3,4 Human flu vaccines are re-formulated frequently (often yearly) to ensure they are representative of circulating strains, with the goal of avoiding vaccine failure due to antigenic drift. 1 The importance of antigenic drift for vaccine efficacy of equine influenza vaccines has also been shown in numerous outbreaks. 3,4,5,7 In the first outbreak of equine influenza in Australia in 2007, the initial spread of the virus in the general population was linked to a "one-day event" at Maitland, New South Wales, in mid-August. By December, when the last case was reported, more than 76,000 horses on over 10,000 properties were reported as infected. 3 Typically, young horses, horses with low serum antibody titers, and those that are highly mobile and commingle with large groups of horses are considered most at risk. The strong correlation between antibody levels and protection requires a reasonably close homology between the vaccine and the challenge virus. 4,10 Horses require higher antibody levels to be protected against heterologous strains of H3N8 virus. 3,4,10 Therefore, a "mismatch" between vaccine and infecting strains requires higher levels of antibodies to prevent infection and significantly increases the risk of an outbreak at the population level. The greater the antigenic distance, or "mismatch," between a vaccine strain and the field virus encountered by a horse, the greater the chance that the horse will become infected. Many cross-protection 1 studies have been conducted in recent years, providing a body of experimental data that support this fact. 3,4,9,10 The continuous evolution and change of equine influenza virus is of major concern. 2, 3,8,9,10 A subclinically affected vaccinated horse is more likely to shed virus if there is a "mismatch" between the field virus and those in the vaccine. 4 Protection against virus shedding is particularly important when introducing vaccinated horses into a susceptible population. The ability of shedding correlates with the degree of relatedness between the vaccine virus and the challenge virus. 3,4 Higher antibody levels have been required for both clinical (clinical signs) and virological (shedding) protection in studies where vaccine strains were antigenically and genetically dissimilar to those circulating in the field (mismatch). When a vaccine "mismatch" occurs vaccinated horses may be afforded some protection from clinical signs of disease, yet those same animals shed live virus resulting in the "population effect" (greater number of animals ill within a population). These horses are a great risk to other horses, especially immunologically naive horses. This scenario was behind the 2007 outbreak of equine influenza in Australia where the introduction of subclinically infected vaccinated horses led to the infection of tens of thousands of horses. The vaccinated horse(s) that introduced influenza into the Australian quarantine facility had been vaccinated with vaccines containing outdated strains, as none of the vaccines available (in those countries) at the time had been updated in line with the OIE recommendations of 2004 (see explanation of OIE below). 5 e q u i n e i n F L u e n z A : T H E I M P A C T O F A n t i g e n i c d r i F t O N v A C C I N E E F F I C A C y ' S steVe grubbs, dVm, Phd, dacVim boehringer-ingelheim

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