ISCOM-based equine influenza vaccine: Duration of immunity and randomised clinical trials to assess an accelerated schedule of immunisation and efficacy

Abstract

a b s t r a c tThe 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 Ò ), 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.

The Immunity Gap Challenge: Protection against a Recent Florida Clade 2 Equine Influenza Strain

“…All of the vaccinates had detectable but low SRH antibody titres at the time of experimental infection. The clinical protection demonstrated in the present study was similar to what has been observed for other EI vaccines when tested much sooner after immunisation, such as at the onset of immunity [ 12 , 25 , 32 , 42 , 43 ] or 2.5 months after V2 [ 14 ]. Virus shedding was measured after individual challenge by nebulisation in the present study, but the overall duration was significantly reduced in the vaccinates compared to the unvaccinated control ponies.…”

“…Despite the significant time between V2 and the experimental infection (i.e., 158 days), the clinical outcome measured in the vaccinated group in the present study was similar to the outcome measured in ponies vaccinated with (1) an EI vaccine based on a canarypox-vectored vaccine expressing the haemagglutinin gene of EIV and experimentally infected with EIV 14 days after the second immunisation [ 35 ] and (2) a whole inactivated EI vaccine as well as experimental infection with EIV 14 or 15 days after V2 [ 12 , 26 ]. The clinical protection achieved in the current study was also similar or superior to the one recorded in ponies vaccinated with an ISCOM-based EI vaccine and experimentally infected with EIV 14 days [ 25 ] or 78 days after V2 [ 14 ], respectively.…”

“…Such an effect is usually not measurable in clinical trials with experimental infection set up at the onset of immunity conferred by vaccination (i.e., experimental infection 2 to 3 weeks after primary immunisation (V1 and V2)). Under such conditions, antibody titres present at the time of experimental infection are usually high enough to significantly limit initial EIV infection, which immediately impacts and reduces the amount of virus shed and detected [ 12 , 25 , 26 , 35 ].…”

“…In the event of an outbreak, and if there is an imminent risk of contact with EIV, boost EI vaccination may need to be considered, especially for horses where the immunisation schedule has been started recently [ 39 ]. While a shortening of the interval between V1 and V2 has been tested [ 25 , 40 , 41 ], an attempt to reduce the gap between V2 and V3 has been shown to be counter-productive, with a long term detrimental effect on humoral immunity induced by V3 and V4 boost immunisations [ 17 ]. This may mean that with current EI vaccine technology it is not possible to close the immunity gap and certainly reducing the interval between V2 and V3 is not recommended.…”

“…Values for internal reference serum standards used during the assay were within the expected range. Serum samples were collected from all ponies on days-1 (V1-1 day) and 56, 69 and 186 (experimental infection) and analysed for tetanus toxoid-binding (ToBI) antibody titre as previously described [ 25 ]. Tetanus toxoid (TT) antibody titres were expressed as international units (IU)/mL of serum.…”