Vaccination against equine influenza: Quid novi?

doi:10.1016/j.vaccine.2006.02.030

Vaccine

Volume 24, Issue 19, 8 May 2006, Pages 4047-4061

https://doi.org/10.1016/j.vaccine.2006.02.030 Get rights and content

Abstract

Equine influenza virus is a leading cause of respiratory disease in the horse. Equine influenza vaccines containing inactivated virus were first developed in the 1960s. Despite their intensive use, equine influenza outbreaks still continue to occur and therefore new strategies of vaccination are necessary to improve vaccine efficacy. Numerous methods of vaccination have been evaluated and commercialised in the horse, the most recent being the cold-adapted influenza virus and poxvirus-based vaccines. As a large animal model, the horse is also a useful species in which to evaluate the potential of new generations of influenza vaccine such as live-attenuated influenza virus engineered by reverse genetics. This report details the equine immune responses conferring protection against influenza. It then undertakes a selective review of different strategies of vaccination against equine influenza that have been developed over the last two decades and discusses factors that may influence the efficacy of vaccination. Finally it outlines progress in the development of a novel vaccination strategy against equine influenza using reverse genetics.

Introduction

Equine influenza A viruses (EIV; H7N7 and H3N8 subtypes) are a leading cause of respiratory disease in the horse. Although the H7N7 influenza virus subtype has not been detected recently, the H3N8 subtype of equine influenza virus has not been controlled successfully by vaccination and remains today a serious threat to horse welfare and an economic problem for the horse industry. Historically, equine influenza vaccines were mainly composed of whole inactivated viruses, which provide protection against influenza through the induction of a short-lived humoral immunity. This is in contrast to immunity stimulated by natural infection, which is more robust and longer lived due to the stimulation of both humoral and cellular immune responses. The development of new strategies of vaccination that mimic more closely the stimulation of the immune system induced by EIV infection, has been the focus of EIV vaccine development in the last two decades. Thus, modern vaccines composed of either live attenuated influenza virus, DNA plasmids or poxvirus-vectors coding for influenza virus proteins were developed and some have been commercialised. Today, a new approach to EIV vaccination using live-attenuated influenza virus engineered by reverse genetics, is also under development. This report will describe the equine influenza virus, its pathogenesis, epidemiology and immunology in the horse and then review different vaccination approaches.

Section snippets

Viral structure

Influenza viruses belong to the family orthomyxoviridae and are classified as A, B and C based on antigenic differences in their nucleoprotein (NP) and matrix (M1) protein. EIV is a type A influenza virus similar to type A human influenza virus. Type A influenza viruses contain segmented RNA (about 13.6 kb) consisting of eight linear, single stranded genomic fragments of negative polarity. Six segments code for single proteins haemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), three

Vaccines against equine influenza virus

The principal aim of influenza vaccination is to reduce clinical signs of the disease, with subsequent improved animal welfare leading to a shortened convalescent period and reducing secondary infections. Reduced shedding of virus has important implications for the spread of infection and is certainly the other major target that should be achieved by vaccination. Vaccination should also provide long-term immunity, an efficient memory response and cross-protection against influenza viruses of

Conclusion

Today, the main types of equine influenza vaccines in use contain whole inactivated virus or subunits. Protection afforded by this first generation of vaccines is based on high levels of protective antibodies. Second generation vaccines (i.e. live attenuated and poxvirus-based vaccines) are now available. These stimulate both humoral and cellular immune responses and so mimic more closely the protective immunity induced by natural infection with influenza virus. These vaccines are not yet

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Epidemiology of equine influenza in the Maghreb area
2022, Comparative Immunology, Microbiology and Infectious Diseases
Equine influenza (EI) is one of the most contagious respiratory infections in horses, donkeys and mules, caused by equine influenza A virus (EIV). It remains a disease with a strong economic stake for the equine industry. This review focuses on the epidemiological situation of EIV in the Maghreb area, which includes Algeria, Morocco and Tunisia. There is serological evidence for extensive circulation of EIV in the Maghreb area since the early 1970s, but reports of detailed investigation of outbreaks are scarce with no documented isolation or molecular characterization of EIV from Tunisia. Isolates of EIV were obtained from outbreaks in Algeria in 1971/1972 and 2011. Similarly, in Morocco, isolates were obtained from outbreaks in 1997 and 2004. The viruses isolated in 2004 showed evidence of ‘evolutionary stasis’, with haemagglutinin and non-structural protein 1 sequences most similar to those of viruses isolated decades earlier. In conclusion, effective surveillance of equids in the Maghreb region, where there is potential for virus re-emergence, should be encouraged.
Equine influenza vaccination as reported by horse owners and factors influencing their decision to vaccinate or not
2020, Preventive Veterinary Medicine
Equine influenza virus is a highly contagious respiratory pathogen that causes pyrexia, anorexia, lethargy and coughing in immunologically naïve horses. Vaccines against equine influenza are available and vaccination is mandatory for horses that participate in affiliated competitions, but this group forms a small proportion of the total horse population. The aims of this study were to: i) identify the equine influenza vaccination rate as reported in 2016 by horse owners in the United Kingdom (UK); ii) examine the demographics of owners and horses which were associated with significantly lower influenza vaccination rates and iii) explore factors that influence horse owners’ decisions around influenza vaccine uptake.
Responses from 4837 UK horse owners who were responsible for 10,501 horses were analysed. An overall equine influenza vaccination rate of 80% (8385/10501) was reported. Several owner demographic characteristics were associated with significantly lower (p<0.05) reported equine influenza vaccination rates including: some geographical locations, increasing horse owner age, annual household income of less that £15,000 and owning more than one horse. Horse-related features which were associated with significantly lower reported equine influenza vaccination rates included age ranges of <4 years and > 20 years, use as a companion or breeding animal or leaving their home premises either never or at most once a year. The most common reasons cited for failing to vaccinate horses was no competition activity, lack of exposure to influenza and expense of vaccines. In contrast, the most common underlying reasons given by horse owners who vaccinated their horse were protection of the individual horse against disease, veterinary advice and to protect the national herd. Owners of vaccinated horses had less previous experience of an influenza outbreak or adverse reaction to vaccination compared with owners of unvaccinated horses.
This study documented a high rate of equine influenza vaccination as reported by owners in a substantial number of horses in the UK, but this does not reflect the level of protection. Sub-populations of horses which were less likely to be vaccinated and the factors that influence each owner’s decision around vaccination of their horses against equine influenza were identified, but may alter following the 2019 European influenza outbreak. This information may nevertheless help veterinary surgeons identify “at-risk” patients and communicate more personalised advice to their horse-owning clients. It may also influence educational campaigns about equine influenza directed to horse owners, which aim to improve uptake of vaccination against this pathogen.
Refinement of the equine influenza model in the natural host: A meta-analysis to determine the benefits of individual nebulisation for experimental infection and vaccine evaluation in the face of decreased strain pathogenicity
2017, Veterinary Microbiology
Equine Influenza (EI) is an important respiratory disease of horses caused by H3N8 equine influenza viruses (EIV). Vaccination is a key strategy to prevent or control this disease. However, EIV undergoes continuous antigenic drift and whilst numerous EI vaccines are commercially available worldwide, an accurate evaluation of their efficacy is frequently required through clinical trials conducted in the natural host. Room nebulisation is one of the chosen methods to challenge horses during EI vaccine studies. A potential decreased pathogenicity observed with recent Florida Clade 2 (FC2) EIV isolates have increased the heterogeneity of the clinical response and virus shedding measured after infection by room nebulisation, which reduced the statistical power of studies. Our objectives were to compare clinical and virological parameters following experimental infection with several different EIV strains and to confirm that individual nebulisation is a model refinement that prevents an increase of the number of animals per group. This study is a retrospective comparison and meta-analysis of clinical and virological results collected from 9 independent EIV infection studies in the natural host. Naïve Welsh mountain ponies were experimentally infected by room or individual nebulisation with FC2 EIV strains, including A/equine/Richmond/1/07 (R/07), A/equine/East Renfrewshire/11 (ER/11), A/equine/Cambremer/1/2012 (C/12) and A/equine/Northamptonshire/1/13 (N/1/13). The retrospective meta-analysis confirmed a decreased pathogenicity of the EIV ER/11 and C/12 strains when compared with R/07. Experimental infection by individual nebulisation improved the clinical and virological parameters induced by recent FC2 strains, when compared with conventional room nebulisation. In conclusion, individual nebulisation offers a better control of the challenge dose administered and a greater homogeneity of the response measured in control animals. This in turn, helps maintain the number of animals per group to the minimum necessary required to obtain meaningful results in vaccine efficacy studies, which adheres to the 3Rs (Replacement, Reduction and Refinement) principles.
Influential factors inducing suboptimal humoral response to vector-based influenza immunisation in Thoroughbred foals
2016, Vaccine
Numerous equine influenza (EI) epizooties are reported worldwide. EI vaccination is the most efficient methods of prevention. However, not all horses develop protective immunity after immunisation, increasing the risk of infection and transmission.
This field study aimed to understand the poor response to primary EI vaccination.
The EI antibody response was measured in 174 Thoroughbred foals set in 3 stud farms (SF#1 to SF#3) over a 2 years period. All foals were immunised with a commercial recombinant canarypox-based EI vaccine. Sera were tested by single radial haemolysis against the A/equine/Jouars/4/06 EIV strain (H3N8) at the time of the first vaccination (V1), 2 weeks and 3 months after the second immunisation (V2), 2 days and 3 months after the third immunisation (V3).
The frequency of poor-responders (no detectable antibody titres) was surprisingly elevated after V2 (56.8%), increased to 81.7% at V2 + 3 months and reached 98.6% at V3. The frequency of poor-responder was still 19.2%, 3 months after V3. Two independent influential factors were identified. The short (V2 + 2 weeks) and mid-term (V2 + 3 months, V3 + 3 months) antibody levels were positively correlated to the age at V1 (p-value = 0.003, 0.031 and 0.0038, respectively). Presence of maternally-derived antibodies (MDA) at V1 was negatively correlated with antibody levels after V3 only (p-value = 0.0056). Given that SF#1 antibody response was below clinical protective levels at all-time points studied, the annual boost immunisation (V4) was brought forward by 7.0 ± 1.1 months. V1 was delayed by 7 weeks the following year, which significantly increased short- and mid-term antibody titres (p-value = 9.9e−07 and 2.31e−07, respectively).
The age and MDA at first immunisation with the canarypox-based IE vaccine play an independent role in the establishment of antibody levels. This study also highlights the benefit provided by serological surveillance to evaluate herd immunity and to implement corrective management/vaccination measures.
ISCOM-based equine influenza vaccine: Duration of immunity and randomised clinical trials to assess an accelerated schedule of immunisation and efficacy
2015, Trials in Vaccinology
The widespread use of equine influenza (EI) vaccines plays an important role in the prevention and control of EI outbreaks. Vaccine strain updates, optimisation of immunisation schedules, and frequent evaluation of vaccine efficacy are necessary to maintain an acceptable level of protection and overall disease control. Results from three independent vaccine studies are reported here.
Study 1: duration of immunity (exploratory research). The antibody and interferon (IFN) gamma response induced by an ISCOM (Immuno-Stimulating COMplex)-based EI vaccine (Equip F®), was measured in a group of 4 ponies up to one year after booster immunisation and compared to immunity induced by equine influenza virus (EIV) infection. The antibody and IFN gamma responses kinetics were defined and levels were similar to those induced by experimental EIV infection.
Study 2: accelerated schedule of immunisation (randomised trial). Most EI vaccines require a 4–6 week interval during the primary two dose course of immunisation, during which time most animals remain susceptible to EIV infection. The immunogenicity and safety of the ISCOM-based EI + tetanus vaccine (Equip FT) with a 3-week accelerated immunisation interval was evaluated and compared to the recommended six-week vaccination interval in order to improve flexibility and to reduce the period of susceptibility. The antibody responses to the vaccine antigens (tetanus toxoid and EIV) were measured up to 2 weeks after the first booster vaccination (V3). The 3-week accelerated primary course interval was well tolerated and serology results suggested good immunogenicity against both EIV and tetanus antigens.
Study 3: efficacy against Florida clade 2 EIV strain (randomised trial). Efficacy against the representative Florida clade 2 strain A/eq/Richmond/1/07 was also evaluated at the peak of immunity, shortly after 2nd vaccination (V2). Six ponies were vaccinated with EquipFT according to label (6-week interval between first and second injection) and 6 control ponies received saline injections. Sixteen days after V2 (day 58), all animals were experimentally infected with A/eq/Richmond/1/07. Clinical signs of disease and virus shedding were assessed for 14 days and found to be significantly reduced in vaccinated animals.
Primary vaccination against equine influenza in foals: when, how and with what? - Overview of the current scientific status
2024, Pferdeheilkunde

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ReviewVaccination against equine influenza: Quid novi?

Abstract

Introduction

Section snippets

Viral structure

Vaccines against equine influenza virus

Conclusion

Vet Clin North Am Equine Pract

Virology

Vet Microbiol

Vaccine

Vet Immunol Immunopathol

Vaccine

Vet Immunol Immunopathol

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Virology

Vet Immunol Immunopathol

Vaccine

Vaccine

Vaccine

Virology

Vet J

Vaccine

Vet Clin North Am Equine Pract

Dev Comp Immunol

Orthomyxoviridae

The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function

J Virol

The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins

EMBO J

Equine influenza

Influenza infections

Experimental infection of ponies with equine influenza A2 (H3N8) virus strains of different pathogenicity elicits varying interferon and interleukin-6 responses

Viral Immunol

Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls

J Virol

Pandemic threat posed by avian influenza A viruses

Clin Microbiol Rev

Isolation of a virus causing respiratory disease in horses

Acta Virol

Characterization of A/eq-1 virus isolated during the equine influenza epidemic in India

Acta Virol

An outbreak of equine influenza type 1 in Egypt in 1989

Vet Med J Giza

Serological evidence for the presence of A/equine-1 influenza virus in unvaccinated horses in Croatia

Vet Rec

A new influenza virus associated with equine respiratory disease

J Am Vet Med Assoc

Transmission of equine influenza virus to dogs

Science

The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population

Proc Biol Sci

Comparison of hamster and pony challenge models for evaluation of effect of antigenic drift on cross protection afforded by equine influenza vaccines

Equine Vet J

Conclusions and recommendations from the consultation of OIE and WHO experts on equine influenza, Newmarket, United Kingdom, September 18–19, 1995

OIE Bull

Defense mechanisms against influenza virus infection in the respiratory tract mucosa

Jpn J Infect Dis

The role of interleukin-6 in mucosal IgA antibody responses in vivo

Science

Nasopharyngeal, tracheobronchial, and sytemic immune responses to vaccination and aerosol infection with equine-2 influenza A virus (H3N8)

Equine immunity to viruses

Vet Clin North Am Equine Pract

M cells and associated lymphoid tissue of the equine nasopharyngeal tonsil

Equine Vet J

Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies

J Virol

Review
Vaccination against equine influenza: Quid novi?