UPDATE ON EQUINE FLU VACCINES

Vet Times The website for the veterinary profession https://www.vettimes.co.uk UPDATE ON EQUINE FLU VACCINES Author : Andy Durham Categories : Vets Date : February 20, 2012 Andy Durham discusses the latest thinking on approaches to influenza, with reference to technology, choosing a product and legal considerations MAJOR antigenic changes in equine influenza viruses over the years has led to the decline of several once-prevalent virus lineages and left us with the present-day threat from H3N8 Equi-2 Florida strains, which are divided into clades 1 and 2 ( Figure 1 ). Around nine or 10 localised outbreaks of equine influenza occur annually in the UK, primarily in unvaccinated horses, although more widespread influenza outbreaks have occurred in both unvaccinated and vaccinated animals in 1989 and 2003. In both of these instances of vaccine breakdown, the virus strains used in licensed equine influenza vaccines at the time were 10 years old. The most up-to-date strains in three of four UK vaccine brands are 14 to 19 years old ( Table 1 ). Which vaccine? In the UK, four licensed equine influenza vaccines are available ( Table 1 ), all having satisfied regulatory bodies in terms of their efficacy and safety to obtain a marketing authorisation. However, the ever-changing challenge presented by a highly mutagenic virus creates a unique pressure for product updates. Vaccine selection by equine practitioners would ideally be based on comparative efficacy in 1 / 5

protecting against viral challenge, although in reality such trials are unlikely to be performed. Consequently, we are exposed to a bombardment of marketing literature and equivocal studies, in which each vaccine manufacturer claims its product has special attributes to warrant its selection. Fortunately, for the busy practitioner without the time to perform his or her own in-depth research, there is an independent source of expert opinion on which to guide our choice. The World Organisation for Animal Health (OIE) expert surveillance panel (ESP) on equine influenza vaccine composition meets annually to review and consider equine influenza activity and disease outbreaks, and publish a recommendation specifying influenza strains it considers appropriate for protection against the current threat. Compliance by vaccine manufacturers is voluntary and, as such, has been disappointing historically, to say the least. Following the UK and South African equine influenza outbreaks in 2003, the ESP met the following year and recommended updating influenza vaccines to contain a Florida clade 1 virus similar to South Africa 03 or Ohio 03. To date, eight years on from that recommendation, three of the four UK equine influenza vaccines still do not comply (Duvaxyn IE plus, Equilis prequenza and Equip F, Table 1 ). In 2010, following recognition of increasing activity attributable to Florida clade 2 viruses, the ESP updated its recommendation to include representatives of both Florida clade 1 (South Africa 03 or Ohio 03) and Florida clade 2 viruses (Richmond 07). Two years on from the 2010 recommendation, no current UK vaccine complies, although assurance of active research and development of strain updates has been made unofficially by at least two manufacturers. Protection against currently circulating equine influenza strains In 2009, Florida clade 1 strains predominated in UK equine influenza outbreaks, and these strains are still regarded as a threat by the ESP. However, the major threat in the UK comes from Florida clade 2 viruses, which have no representative in any UK vaccine. Although one UK brand recently provided evidence of cross protection against Richmond 07 virus (Florida clade 2) with its Newmarket/1/ 93 strain (Duvaxyn IE plus, Elanco), it should be borne in mind that demonstration of protection was with reference to unvaccinated animals, and that challenge with the Richmond 07 virus was conducted only two weeks after the primary vaccination course. Durability of the protection was not tested. The ESP is unambiguous in its recommendation that Florida clade 1 and 2 virus strains should be included in modern vaccines, and specifically criticised older strains, such as Newmarket/1/ 93. 2 / 5

Vaccine technology There are other important attributes of vaccines that seek to augment the immune response to the virus antigen. Duvaxyn IE and Equip F contain killed whole virus mixed with adjuvants, Equilis prequenza contains equine influenza haemagglutinin (HA) incorporated into an ISCOM matrix, while Proteq-flu contains live canarypox virus into which the genome encoding the equine influenza HA antigen has been inserted (vectored vaccine). Cell-mediated immunity (CMI), characterised by cytotoxic T-lymphocyte destruction of virusinfected cells before they release multiplying virions, is generally regarded as offering the best defence against non-viraemic infections, such as equine influenza. Killed virus particles would be expected to be processed via the exogenous pathway by antigenpresenting cells and T-helper lymphocytes, with the preferential generation of a humoral antibody response. Indeed, an Irish study (of products mostly different from those in the UK) showed an adjuvanted killed virus vaccine to stimulate especially high antibody responses. Inclusion of an ISCOM matrix may increase the likelihood of achieving CMI, and evidence of such has been published. However, live influenza virus infection and live-vectored vaccines would be expected to elicit optimal CMI after processing via the endogenous pathway due to intracellular synthesis of virus antigen. Legal issues Under the Veterinary Medicines Regulations we are obliged to administer vaccinations in accordance with their marketing authorisations. Any divergence from the data sheets should be based on sound clinical reasons and might constitute a criminal offence. Two common circumstances exist where veterinary surgeons may be tempted to administer vaccines off-label, with dubious justification. Firstly, the timing of vaccination involves the attempted reconciliation of the legal requirements, as outlined in the product data sheets and the regulatory requirements contained in British Horse Association (BHA) and Fédération Equestre Internationale (FEI) rules ( Figure 2 ). However, these are frequently incompatible with one another. For example, administration of the second dose of a primary course 90 days after the first (acceptable to BHA and FEI) would constitute off-label usage, which might be hard to defend if required to do so (such as following vaccine breakdown). Furthermore, the data sheet recommendation to administer the first booster vaccination at five months after the primary course for three of the four current UK vaccines would not strictly satisfy FEI rules (six months plus or minus 21 days). A second potential legal pitfall occurs when faced 3 / 5

with a vaccination record containing multiple vaccine brands. Two vaccine brands (Duvaxyn IE and Equip F) recommend they are not used interchangeably with other brands, unless they contain the same vaccine strains. Conclusions In the UK, equine influenza viruses circulate frequently, yet all vaccine brands contain less than optimal virus strains. The current threat is from viruses from Florida clades 1 and 2, yet only one vaccine brand contains a representative antigen from Florida clade 1 (Proteq-flu: Ohio 03), and none yet contain a recommended clade 2 strain (Richmond 07). The history of non-compliance by vaccine manufacturers to OIE recommendations is disquieting and appears only likely to change with commercial pressure from veterinary surgeons and horse owners exercising vaccine brand selection according to sound scientific principles applied to up-todate surveillance data. Further reading Cullinane A et al (2010). Equine influenza surveillance and control, Influenza and Other Respiratory Viruses 4(6): 339-344. Daly J M et al (2011). Equine influenza: a review of an unpredictable virus, The Veterinary Journal 189(1): 7-14. DEFRA/AHT/BEVA Equine Quarterly Disease Surveillance Reports, www.aht.org.uk/equine_disease.html Elton D and Bryant N (2011). Facing the threat of equine influenza, Equine Veterinary Journal 43(3): 250-254. Lewis N S et al (2011). The antigenic and genetic evolution of equine influenza A (H3N8) virus from 1968-2007, Journal of Virology 85(23): 12,742-12,749. Mumford J (2009). The Equine Influenza Expert Surveillance Panel. AHT/BEVA/DEFRA Equine Quarterly Disease Surveillance Report 5(3) www.aht.org.uk National Office of Animal Health Compendium of Data Sheets www.noahcompendium.co.uk/therapeutic_indication/therapeutic_indication/-142.html Paillot R et al (2006). Vaccination against equine influenza: quid novi? Vaccine 24(19): 4,047-4,061. The World Organisation for Animal Health (OIE) reports from the OIE Expert Surveillance Panel on Equine Influenza Vaccines (included in bulletins published from the 2nd quarter of each year), www.oie.int/publications-and-documentation/bulletins-online 4 / 5

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