Foot-and-mouth disease and the African buffalo (Syncerus caffer). : II. Virus excretion and transmission during acute infection

Three groups of young buffalo in captivity were infected by exposing them to similar buffalo in the acute stages of infection induced by needle inoculation with SAT 1 or 2 viruses. Clear foot lesions developed in most of the buffalo from which the relevant virus types were re-isolated. During the first week following infection virus was found in blood, nasal secretions, saliva, preputial secretions and faeces. Air samples collected in the immediate vicinity of acutely infected buffalo were also found to contain virus. However, the regularity of virus detection as well as the quantity of virus in buffalo specimens was generally lower than for cattle infected with viruses of the same type. Conversely, virus was detected in the nasal secretions or saliva of 3 buffalo up to 4 weeks after infection, a situation which has not been encountered in cattle. Susceptible cattle and impala (Aepyceros melampus) were penned together with or in the immediate vicinity of infected buffalo and shared feeding and watering facilities with the buffalo. The pattern of transmission which emerged indicated that transfer of these viruses from buffalo to other species probably occurs only in the acute stages of infection and where there is direct physical contact between the speciesThe articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge

The genetic diversity of the three Southern African Territories (SAT) types of foot-and-mouth diseasevirus (FMDV) reflects high antigenic variation, and indications are that vaccines targeting each SAT-specific topotype may be needed. This has serious implications for control of FMD using vaccines as wellas the choice of strains to include in regional antigen banks. Here, we investigated an intra-serotypechimeric virus, vSAT2ZIM14-SAT2, which was engineered by replacing the surface-exposed capsid-codingregion (1B-1D/2A) of a SAT2 genome-length clone, pSAT2, with that of the field isolate, SAT2/ZIM/14/90.The chimeric FMDV produced by this technique was viable, grew to high titres and stably maintained the1B-1D/2A sequence upon passage. Chemically inactivated, oil adjuvanted vaccines of both the chimericand parental immunogens were used to vaccinate cattle. The serological response to vaccination showedthe production of strong neutralizing antibody titres that correlated with protection against homolo-gous FMDV challenge. We also predicted a good likelihood that cattle vaccinated with an intra-serotypechimeric vaccine would be protected against challenge with viruses that caused recent outbreaks insouthern Africa. These results provide support that chimeric vaccines containing the external capsid offield isolates induce protective immune responses in FMD host species similar to the parental vaccine.MSD Animal Health (previously Intervet SPAH)http://www.elsevier.com/locate/vaccine2016-06-30hb201

Tracking the antigenic evolution of foot-and-mouth disease virus

Quantifying and predicting the antigenic characteristics of a virus is something of a holy grail for infectious disease research because of its central importance to the emergence of new strains, the severity of outbreaks, and vaccine selection. However, these characteristics are defined by a complex interplay of viral and host factors so that phylogenetic measures of viral similarity are often poorly correlated to antigenic relationships. Here, we generate antigenic phylogenies that track the phenotypic evolution of two serotypes of footand- mouth disease virus by combining host serology and viral sequence data to identify sites that are critical to their antigenic evolution. For serotype SAT1, we validate our antigenic phylogeny against monoclonal antibody escape mutants, which match all of the predicted antigenic sites. For serotype O, we validate it against known sites where available, and otherwise directly evaluate the impact on antigenic phenotype of substitutions in predicted sites using reverse genetics and serology. We also highlight a critical and poorly understood problem for vaccine selection by revealing qualitative differences between assays that are often used interchangeably to determine antigenic match between field viruses and vaccine strains. Our approach provides a tool to identify naturally occurring antigenic substitutions, allowing us to track the genetic diversification and associated antigenic evolution of the virus. Despite the hugely important role vaccines have played in enhancing human and animal health, vaccinology remains a conspicuously empirical science. This study advances the field by providing guidance for tuning vaccine strains via site-directed mutagenesis through this high-resolution tracking of antigenic evolution of the virus between rare major shifts in phenotype.S1 Data. VNT serological results for serotype O viruses and antisera.S2 Data. LPBE serological results for serotype O viruses and antisera.S3 Data. VNT serological results for serotype SAT1 viruses and antisera.S1 Table. Foot-and-mouth disease virus details with accession numbers.S2 Table. Pan-serotypic reference alignment of FMDV. The dataset shows the aligned VP2, VP3 and VP1 proteins of example SAT1 and O isolates used in the study alongside representative isolates from the other five serotypes. The four contiguous surface-exposed structural motifs confirmed as containing antigenic sites on at least four serotypes are highlighted in red–locations are approximate due to structural differences between the serotypes. The RGD cell surface receptor-binding motif, in the centre of the third site, is highlighted in blue.S3 Table. Residues identified as part of epitopes on structural proteins across the six tested serotypes of FMDV, along with corresponding positions on all serotypes.S4 Table. SAT1 mar-mutants.The authors acknowledge the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme on Livestock Viral Diseases at The Pirbright Institute (BB/J004375/1) [RR SP DJP MM] and BBSRC BB/ G529532/1 [DWB MM], BB/F009186/1 [MM] and BBSRC BB/L004828 [RR] and BBSRC / Department for International Development / Scottish Government grants BB/H009302/1 [RR] and BB/H009175/1 [SP FFM RR] (http://www.bbsrc.ac.uk), and Department for Environment, Food and Rural Affairs grant SE2937 (http://www.gov.uk/defra) [MM]. The Food and Agriculture Organisation financially supported the research to determine one-way relationship and antigenic relatedness of SAT1 viruses under grants OSRO/RAF/721/EC and MTF/INT/003/EEC (http:// www.fao.org) [FFM AL JJE BB], and RMRSA (http:// www.rmrdsa.co.za) (Improving detection and characterisation methods for FMDV and ASFV for cattle and pigs in the SADC region) [BB]. Structural studies supported by the UK Medical Research Council grant MR/N00065X/1 [EEF] (http://www.mrc. ac.uk). The work of the Wellcome Trust Centre in Oxford is supported by the Wellcome Trust core award 090532/Z/07/Z [EEF] (http://www.wellcome.ac. uk).http://www.plosone.orgam2016Microbiology and Plant PathologyProduction Animal Studie

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

Experimental infection of giraffe (Giraffa camelopardalis) with SAT-1 and SAT-2 foot-and-mouth disease virus

The potential role of giraffe (Giraffa camelopardalis) in the epidemiology and spread of foot-and-mouth disease (FMD) SAT types was investigated by experimental infection and detection of virus in excretions using virus isolation on primary pig kidney cell cultures. In two experiments separated by a period of 24 months, groups of four animals were needle infected with a SAT-1 or SAT-2 virus, respectively and two in-contact controls were kept with each group. Viraemia was detected 3–9 days post-infection and virus isolated from mouth washes and faeces only occasionally up to day 13. The SAT-1 virus was transmitted to only one in-contact control animal, probably via saliva that contained virus from vesicles in the mouth of a needle-infected animal. None of the animals infected with the SAT-2 virus had any vesicles in the mouth, and there was no evidence of transmission to the in-contact controls. No virus was detected in probang samples for the duration of the experiments (60 days post-infection), indicating that persistent infection probably did not establish with either of these isolates. Giraffe most likely do not play an important role in FMD dissemination. Transmission of infection would possibly occur only during close contact with other animals when mouth vesicles are evident

Parametrische Inferenz unter Vorschaltung von Ausreissertests

SIGLETIB Hannover: RN 6494(1980,2) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Antigenic evolution of Serotypes O and SAT1.

<p>Phylogeny of all serotype O viruses (a) and serotype SAT1 (b) are shown with shading and labelling of topotypes as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.g001" target="_blank">Fig 1A–1B</a>. Different branch colours denote antigenic dissimilarity with respect to VNT between the viruses derived from analyses of the sequence and serological data and ancestral state reconstruction. Conversely, the same colours in the same phylogeny denote the same antigenic phenotype. ⁺Change in antigenic phenotype for which no causative substitution has been identified. The broadest such group defined by VNT is starred for serotype O (spanning 5 topotypes) and SAT1 (spanning 2 topotypes). As in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.g001" target="_blank">Fig 1</a>, phylogenies are time-resolved, with branch lengths measured in evolutionary time rather than substitutions.</p

Phylogenetic tree for serotypes O and SAT1.

<p>(a) Phylogeny of all serotype O viruses studied, with alternate shading showing geographically-isolated subtypes (topotypes), labelled with their names in red (1, 2, 3 and 4 are East Africa topotypes EA-1, EA-2, EA-3 and EA-4, and W is the West Africa topotype, WA). The three unshaded viruses are all sole representatives of their topotype. (b) Phylogeny of all serotype SAT1 viruses studied (including those from[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.ref025" target="_blank">25</a>]), with alternate shading showing topotypes, labelled with their numbers in red. The two unshaded viruses are sole representatives of their topotype. Phylogenies are time-resolved, with branch lengths measured in evolutionary time rather than substitutions.</p

Antigenic impact of introduced substitutions on VNT and LPBE titres.

<p>Antigenic impact of introduced substitutions on VNT and LPBE titres.</p

Antigenic sites on serotypes O and SAT1.

<p>The molecular surface of (a) serotype O and (b) serotype SAT1 icosahedral protomers is shown using pymol (Schrödinger LLC), with the molecular surface of neighbouring protomers shown as a light grey mesh (refer to inset icosahedral representation of an FMDV capsid for orientation). The molecular surface is white, with known antigenic sites on this serotype in orange (red when they were identified in this study), and known antigenic sites for any other serotype in yellow (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.t001" target="_blank">Table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.s006" target="_blank">S3 Table</a> for details). The location of the residues on the VP1 βG-βH loop could not be resolved on the serotype SAT1 structure, and so sites on that loop are not shown. Blue highlights mark the beginning (VP1 139) and end (VP1 165, with pale dot) of the disordered area, and the approximate locations of all four surface-exposed regions identified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159360#pone.0159360.t001" target="_blank">Table 1</a> are also circled in blue and marked as before with *1-*4. Residues identified in this study but not in these regions are individually labelled with their positions on the common alignment. The three-fold and five-fold axes of symmetry are shown by triangles and pentagons respectively.</p