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Reduction of foot-and-mouth disease virus transmission in cattle vaccinated one or two weeks before challenge using a commercial polyvalent vaccine.

ABSTRACT: Immediate vaccination of the most susceptible and epidemiological relevant animals is a crucial part of control measures that facilitate virus elimination in case of entry of foot-and-mouth disease (FMD). The objective of this study was to evaluate the effect of cattle vaccination 7 and 14 days prior challenge using a vaccine commonly applied in systematic vaccination campaigns against transmission of FMD virus (FMDV). Transmission of FMDV was investigated in three groups of ten cattle each: one non-vaccinated group and two groups that were either vaccinated 7 days (-7/vaccinated group) or 14 days (-14/vaccinated group) before intranasal (IN) inoculation. Five cattle heads from each group were inoculated using the IN-route with the A/Argentina/2001 FMDV strain, while the remaining five cattle heads of each group were contact-exposed to inoculated cattle. Clinical signs were recorded; virus isolation and genome detection by RT-PCR were carried out on oesophageal-pharyngeal fluid (OPF) and blood. Neutralizing antibody titers and antibodies against non-structural proteins (NSP) of FMDV were also determined. Results suggest that the experimental design, virus challenge dose, and virus infectivity were appropriate and that the virus had been transmitted to naïve calves. Under the outlined experimental conditions, vaccination 7 and 14 days prior to challenge induced full clinical protection against virus inoculation. Moreover, -7/ or -14/vaccinated calves that had been contact-exposed to -7/ or -14/vaccinated IN-challenged calves, did not become infected. Consequently, no virus transmission occurred from vaccinated and subsequently infected calves to cohabitating vaccinated calves (R = 0). According to our results, early vaccination during an outbreak is effective as virus transmission can be significantly reduced using a vaccine commercially available, routinely applied in systematic vaccination campaigns.

SUBMITTER: Duffy S

PROVIDER: S-EPMC7190753 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Reduction of foot-and-mouth disease virus transmission in cattle vaccinated one or two weeks before challenge using a commercial polyvalent vaccine.

Duffy Sergio S Fondevila Norberto N Galdo Novo Sabrina S Aznar María M Garro Carlos C Smitsaart Eliana E Monti Gustavo G

Vaccine: X 20200413

Immediate vaccination of the most susceptible and epidemiological relevant animals is a crucial part of control measures that facilitate virus elimination in case of entry of foot-and-mouth disease (FMD). The objective of this study was to evaluate the effect of cattle vaccination 7 and 14 days prior challenge using a vaccine commonly applied in systematic vaccination campaigns against transmission of FMD virus (FMDV). Transmission of FMDV was investigated in three groups of ten cattle each: one ...[more]

PMID: 32368734

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Project description:A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicle-associated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+/MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+/CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of epithelial cells of the nasopharyngeal mucosa that could enable shedding and long-term persistence of infectious virus. Additionally, these data indicate different mechanisms within the immediate host response to infection between non-vaccinated and vaccinated cattle.

Project description:There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV.IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD-free countries, which have prohibited the import of FMDVs.

Project description:Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was simultaneously infected with both viruses, while additional cohorts were initially infected with FMDV A and subsequently superinfected with FMDV O after 21 or 35 days. Coinfections were confirmed during acute infection, with both viruses concurrently detected in blood, lesions, and secretions. Staggered exposures resulted in overlapping infections as convalescent animals with persistent subclinical FMDV infection were superinfected with a heterologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected following the heterologous virus exposure. This effect was transient, as all animals superinfected at 35 days post-initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. Analysis of viral genomes confirmed interserotypic recombination events within 10 days in the upper respiratory tract of five superinfected animals from which the dominant genomes contained the capsid coding regions of the O virus and nonstructural coding regions of the A virus. In contrast, there were no dominant recombinant genomes detected in samples from simultaneously coinfected cattle. These findings inculpate persistently infected carriers as potential FMDV mixing vessels in which novel strains may rapidly emerge through superinfection and recombination. IMPORTANCE Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas of endemic FMD suggest that animals can be simultaneously infected by more than one distinct variant of FMD virus (FMDV), potentially resulting in emergence of novel viral strains through recombination. However, there has been limited investigation of the mechanisms of in vivo FMDV coinfections under controlled experimental conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct serotypes of FMDV, with different outcomes associated with the timing of exposure to the two different viruses. Additionally, dominant interserotypic recombinant FMDVs were discovered in multiple samples from the upper respiratory tracts of five superinfected animals, emphasizing the potential importance of persistently infected FMDV carriers as sources of novel FMDV strains.

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Reduction of foot-and-mouth disease virus transmission in cattle vaccinated one or two weeks before challenge using a commercial polyvalent vaccine.

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Reduction of foot-and-mouth disease virus transmission in cattle vaccinated one or two weeks before challenge using a commercial polyvalent vaccine.

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