Dataset Information

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.

SUBMITTER: Paillot R

PROVIDER: S-EPMC6161116 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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

Paillot Romain R Garrett Dion D Lopez-Alvarez Maria R MR Birand Ihlan I Montesso Fernando F Horspool Linda L

Vaccines 20180702 3

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 ...[more]

PMID: 30004410

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Project description:Every year, several epizooties of equine influenza (EI) are reported worldwide. However, no EI case has been identified in France between 2015 and late 2018, despite an effective field surveillance of the pathogen and the disease. Vaccination against equine influenza virus (EIV) remains to this day one of the most effective methods to prevent or limit EI outbreaks and the lack of detection of the pathogen could be linked to vaccination coverage. The aim of this study was to evaluate EI immunity and vaccine coverage in France through a large-scale serological study. A total of 3004 archived surplus serums from French horses of all ages, breeds and sexes were selected from four different geographical regions and categories (i.e., sanitary check prior to exportation, sale, breeding protocol or illness diagnosis). EIV-specific antibody response was measured by single radial hemolysis (SRH) and an EIV-nucleoprotein (NP) ELISA (used as a DIVA test). Overall immunity coverage against EIV infection (i.e., titers induced by vaccination and/or natural infection above the clinical protection threshold) reached 87.6%. The EIV NP ELISA results showed that 83% of SRH positive serum samples from young horses (≤3 years old) did not have NP antibodies, which indicates that the SRH antibody response was likely induced by EI vaccination alone (the HA recombinant canarypoxvirus-based EI vaccine is mostly used in France) and supports the absence of EIV circulation in French horse populations between 2015 and late 2018, as reported by the French equine infectious diseases surveillance network (RESPE). Results from this study confirm a strong EI immunity in a large cohort of French horses, which provides an explanation to the lack of clinical EI in France in recent years and highlights the success of vaccination against this disease. However, such EI protection has been challenged since late 2018 by the incursion in the EU of a Florida Clade 1 sub-lineage EIV (undetected in France since 2009), which is also reported here.

Project description:BackgroundEquine influenza is an important cause of respiratory disease in equids. The causative virus; EIV, is highly variable and can evolve by accumulation of mutations, particularly in the haemagglutinin (HA) gene. Currently, H3N8 is the sole subtype circulating worldwide with Florida clade 1 (FC1) is most prevalent in the Americas and FC2 in Asia and Europe. In Egypt, EIV was detected in two occasions: subtype H7N7 in 1989 and subtype H3N8 (FC1) in 2008. No data is available on the circulation pattern of EIV during the last decade despite frequent observation of suspected cases.MethodsTwenty-two nasal swabs were collected from vaccinated and non-vaccinated horses showing respiratory signs suggestive of EIV infection in 2017-18. Three additional swabs were retrieved during a national race event in January 2018 from Arabian mares with high fever, gait stiffness and dry cough. Samples were screened by RT-qPCR and HA1 domain of the hemagglutinin gene was amplified and sequenced for sequence and phylogenetic analysis.ResultsRT-qPCR screening revealed that only the 3 samples from the race were positive with cycle thresholds ranging from 16 to 21 indicating high viral load. Isolation attempts in hen's eggs were unsuccessful. Sequence analysis of the HA1 domain gene has revealed two identical nucleotide sequences, while the third contained 3 synonymous mutations. Phylogenetic analysis clustered study sequences with recent FC2 sequences from Europe. Amino acid alignments revealed 14 and 13 amino acid differences in the study sequences compared to A/equine/Egypt/6066NANRU-VSVRI/08 (H3N8) and A/equine/Kentucky/1997 (H3N8), respectively, available as EIV vaccines in Egypt. Nine amino acids were different from A/equine/Richmond/1/2007 (H3N8), the recommended FC2 vaccine strain by the world organization of animal health expert surveillance panel (OIE-ESP), two of which were unique to the Egyptian sequences while the remaining 7 changes were shared with the FC2-144V subgroup detected in the United Kingdom from late 2015 to 2016.ConclusionsThe study represents the first reported detection of FC2-144V related EIV from Arabian mares in Egypt, and probably from the entire middle east region. The presented information about EIV epidemiology and spread may require reconsideration of the vaccine strains used in the national vaccination programs.

Project description:BackgroundThe availability of H5N1 vaccines that can elicit a broad cross-protective immunity against different currently circulating clade 2 H5N1 viruses is a pre-requisite for the development of a successful pre-pandemic vaccination strategy. In this regard, it has recently been shown that adjuvantation of a recombinant clade 1 H5N1 inactivated split-virion vaccine with an oil-in-water emulsion-based adjuvant system also promoted cross-immunity against a recent clade 2 H5N1 isolate (A/Indonesia/5/2005, subclade 2.1). Here we further analyse the cross-protective potential of the vaccine against two other recent clade 2 isolates (A/turkey/Turkey/1/2005 and A/Anhui/1/2005 which are, as defined by WHO, representatives of subclades 2.2 and 2.3 respectively).Methods and findingsTwo doses of the recombinant A/Vietnam/1194/2004 (H5N1, clade 1) vaccine were administered 21 days apart to volunteers aged 18-60 years. We studied the cross-clade immunogenicity of the lowest antigen dose (3.8 microg haemagglutinin) given with (N = 20) or without adjuvant (N = 20). Immune responses were assessed at 21 days following the first and second vaccine doses and at 6 months following first vaccination. Vaccination with two doses of 3.8 microg of the adjuvanted vaccine induced four-fold neutralising seroconversion rates in 85% of subjects against A/turkey/Turkey/1/2005 (subclade 2.2) and 75% of subjects against A/Anhui/1/2005 (subclade 2.3) recombinant strains. There was no response induced against these strains in the non-adjuvanted group. At 6 months following vaccination, 70% and 60% of subjects retained neutralising antibodies against the recombinant subclade 2.2 and 2.3 strains, respectively and 40% of subjects retained antibodies against the recombinant subclade 2.1 A/Indonesia/5/2005 strain.ConclusionsIn addition to antigen dose-sparing, adjuvantation of inactivated split H5N1 vaccine promotes broad and persistent cross-clade immunity which is a pre-requisite for a pre-pandemic vaccine.Trial registrationClinicalTrials.gov NCT00309634.

Dataset Information

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

Publications

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

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