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

Abstract

Vaccination is one of the most effective tools for limiting the impact of equine influenza (EI). The humoral immunity established following a primary vaccination course can decrease significantly between the second (V2) and third immunisations (V3), leaving some horses insufficiently protected for several weeks. This so-called “immunity gap” poses a challenge to all EI vaccines. During this period, the EI infection of vaccinated animals may be followed by marked clinical signs and virus shedding. However, several EI vaccines have been shown to stimulate equine influenza virus (EIV)-specific cell-mediated immunity, which is likely to play a role in protection against EIV infection and/or mitigate the clinical and virological signs of EI. Reducing the interval between V2 and V3 has been shown to be counterproductive to longer-term immunity. Further research is needed to define and address the “immunity gap” in horses. This study aimed to measure the level of protection induced by a whole inactivated, ISCOMatrix adjuvanted, EI and tetanus vaccine (Equilis Prequenza-Te) when challenged during the immunity gap (i.e., immediately before the recommended boost immunisation, more than 5 months after V2) using infection with a recent heterologous Florida Clade 2 (FC2) equine influenza virus (EIV) strain. This vaccine was tested in a Welsh mountain pony model. A group of seven ponies was vaccinated twice, 4 weeks apart. The protective antibody response was measured and ponies were challenged, along with 5 unvaccinated control ponies, by experimental infection with the FC2 A/eq/Northamptonshire/1/13 EIV strain, 158 days (around 5.2 months) after V2 and their clinical signs and virus shedding were monitored. EI serology was measured by single radial haemolysis (SRH) and haemagglutination inhibition (HI). Clinical signs and virus shedding (measured by qRT-PCR and hen’s egg titration) were compared with controls. All vaccinates had detectable, low SRH antibody titres and most had detectable, low HI titres. Significant clinical and virological protection was observed in vaccinates (p < 0.05), supporting the good performance of this vaccine against a recent EIV strain. In this study, the impact of the immunity gap in ponies was limited after primary vaccination with this whole inactivated, ISCOMatrix adjuvanted EI and tetanus vaccine (Equilis Prequenza-Te) when infected several months after V2 with a recent FC2 strain, which is representative of EIV circulating in the EU.

Success and Limitation of Equine Influenza Vaccination: The First Incursion in a Decade of a Florida Clade 1 Equine Influenza Virus that Shakes Protection Despite High Vaccine Coverage

“…A possible hypothesis is that horses born in 2016 and 2017 were sampled during their primary course of EI vaccination and may have not yet developed a complete and robust EI humoral immune response at the time of sampling. The results are correlated with a previous field study that highlighted a large frequency of Thoroughbred foals displaying low or negative SRH antibody titers during their primary EI immunization and up to 5 months after the third EI immunization (V3) [27] and other clinical studies highlighting the immunity gap frequently observed in the weeks preceding the third EI immunization [28][29][30]. In the field study, the frequency of seronegative foals (i.e., SRH = 0 mm 2 ) was greater than 25% at different sampling time points during the primary EI immunization (at the time of first immunization, two weeks and three months after the second immunization and two days after the third immunization) [27].…”

Impact of Mixed Equine Influenza Vaccination on Correlate of Protection in Horses

“…The SRH antibody levels measured in weanlings with Equilis ® Prequenza-Te were similar to the antibody response measured in ponies vaccinated with the same EI vaccine in a recent study conducted by Paillot et al (2018) [37]. Significant clinical and virological protections were measured when these ponies were experimentally infected with a recent FC2 EIV strain, five months after V2 [37].…”

“…The other two EI vaccines (Equilis ® Prequenza-TE and Calvenza-03 ® ) contain H3N8 heterologous strains. The cross protection between EIV strains is well documented, as recently demonstrated by Paillot et al (2018) [37]. Gildea et al (2011) [25] found that the humoral antibody response was similar for all vaccines used and, for all antigens tested [25], sera from vaccinated horses were cross-reactive [38].…”

Equine Influenza Virus and Vaccines

“…Closing the immunity gap is a concern, because this is the age in which performance horses from different stables are comingled for training, presenting elevated risk of disease exposure. Different vaccines and vaccination schedules have shown mixed success [ 109 , 110 , 111 ]. Maternal antibody interference with foal EIV vaccinations is a concern, especially with inactivated virus vaccines [ 110 , 112 , 113 , 114 , 115 ], such that the recommended age for the first (priming) dose is typically 6 months in foals whose dams are expected to be EI-seropositive.…”

“…Different vaccines and vaccination schedules have shown mixed success [ 109 , 110 , 111 ]. Maternal antibody interference with foal EIV vaccinations is a concern, especially with inactivated virus vaccines [ 110 , 112 , 113 , 114 , 115 ], such that the recommended age for the first (priming) dose is typically 6 months in foals whose dams are expected to be EI-seropositive. Fortunately, in such foals, maternal antibodies from colostrum are protective, and EI is seldom a problem until after 6 months of age.…”