Foot-and-mouth disease (FMD) is an acute, highly contagious viral disease of domestic and wild cloven-hoofed animals, caused by FMD virus (FMDV). An FMD outbreak can cause major production losses and ...have significant implications for trade. Vaccination can assist in controlling the disease, and emergency vaccination using high antigen payload vaccines (>6 PD50/dose) is considered an important control approach in the event of an outbreak. In recent years there has been a divergence of serotype A viruses in South East Asia (SEA) into several distinct genetic and antigenic clusters. Numerous variants were found to poorly match serotype A vaccines commonly included in international antigen banks. This study examined the ability of single vaccination with high-potency monovalent A22 IRQ vaccine to protect sheep following challenge with the A/VIT/15/2012 strain, just four days following vaccination. The vaccine proved effective at limiting clinical disease but did not prevent infection.
Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used ...in addition to other control measures. However, only a limited number of vaccine strains are commercially available, which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank, to ensure they are prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries with OIE-endorsed FMD control plans who had not reported FMD for many years. In vitro vaccine-matching results showed a poor match (r1-value < 0.3) with the more widely used vaccine strain O1 Manisa and less protection in a challenge test. This paper describes the use of the O3039 vaccine strain as an alternative, either alone or in combination with the O1 Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post-vaccination (to study protection and emergency use) and 21 days post-vaccination (as in standard potency studies). The results indicated that the O3039 vaccine strain alone, as well as the combination with O1 Manisa, is effective against this strain of the O/ME-SA/Ind/2001d lineage, offering protection from clinical disease even after 7 days post-vaccination with a reduction in viraemia and virus excretion.
Over the last 15 years, FMDV serotype A viruses in South-East Asia (A/ASIA/SEA-97 lineage) have diverged into several clusters. Variants from Thailand in 2011-2013 have caused vaccine failures and ...returned poor r
1
-values (<0.30) to A
22
Iraq 64 (A22) and A Malaysia 97 (A May) vaccine strains. We investigated the protective ability of monovalent and bivalent A Malaysia 97 and A22 Iraq 64 vaccine strains against infection with an A/Asia/SEA-97 variant in pigs. Pigs were challenged with a variant of A/Asia/SEA-97 lineage either 21- or 7- days post-vaccination (V21 or V7) using the heal-bulb challenge. Only one in five pigs were protected in the V21 monovalent vaccine groups. Less severe clinical signs were observed in the A22 IRQ group compared to the A MAY 97 group. In the V21 combination group, 4 out of 5 pigs were protected and viraemia was significantly reduced compared to the monovalent V21 groups. V7 vaccine groups were not protected. The neutralising antibody response was below the detection limit in all groups on the challenge day, showing a poor correlation with protection. There was no evidence that the pigs protected from systemic disease had protective antibody responses sooner than other pigs in the study, implying other immune mechanisms might play a role in protecting these animals. FMDV was detected in the nasal and oral swab samples between 1 and 6 dpc. Viral loads were lower in the nasal swab samples from the V21 combination group than the other groups, but there was no difference in the oral swab samples. Since all unvaccinated controls were euthanised by 6-day post-challenge for ethical reasons, the ‘area under the curve (AUC)' method was used to compare the viraemia and virus excretion in different groups. We recommend that for the A/Asia/SEA97 variants, a combination vaccine with A Malaysia 97 and A22 Iraq 64 vaccine strains would be ideal compared to monovalent vaccines.
Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer ...membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36(YdF) virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36(YdF) infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36(YdF) extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5(P189S) mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions.
The combined application of vaccines in swine offers many benefits, including reduced time and labour costs, and improved animal welfare, due to fewer injections and manipulations. This study ...investigated if simultaneous intradermal vaccinations against porcine circovirus 2, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, and Lawsonia intracellularis, using a specialised needle-free applicator would confer comparable protection against experimental infection compared to the single vaccines. In all cases, the administration of the vaccines together was as efficacious as the administration of the vaccines alone, significantly reducing clinical signs associated with each of the four pathogens.
Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine ...for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when
is deleted.
The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their ...utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease.
Since 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East have been caused by a new emerging viral lineage, A/ASIA/G-VII.
vaccine matching data indicated that this virus poorly matched ...(low r
-value) with vaccines that were being used in the region as well as most other commercially available vaccines. The aim of this study was to assess the performance of two candidate vaccines against challenge with a representative field virus from the A/ASIA/G-VII lineage. The results from an initial full dose protection study provided encouraging data for the A/MAY/97 vaccine, while the A
/IRQ/64 vaccine only protected 2/7 vaccinated animals. In view of these promising results, this vaccine was tested in a potency test (PD
) experiment in which 5 cattle were vaccinated with a full dose, 5 cattle with a 1/3 dose and 5 cattle with a 1/9 dose of vaccine. At 21 days post vaccination these vaccinated cattle and 3 control cattle were challenged intradermolingually with a field isolate from the A/ASIA/G-VII lineage. The intra-serotype heterologous potency test resulted in an intra-serotype heterologous potency of 6.5 PD
/dose. These data support previous studies showing that a high potency emergency vaccine can protect against clinical disease when challenged with a heterologous strain of the same serotype, indicating that not only the r
-value of the vaccine, but also the homologous potency of a vaccine should be taken into account when advising vaccines to control an outbreak.
Erbovirus is a genus of the family Picornaviridae and equine rhinitis B virus (ERBV) is the sole species. Erboviruses infect horses causing acute respiratory disease and sub-clinical and persistent ...infections. Despite the high seroprevalence and worldwide distribution of these viruses, the pathogenesis and antigenic structure of the three ERBV serotypes (ERBV1, 2 and 3) is poorly understood. To characterise linear epitopes on ERBV structural proteins, a set of fusion proteins were expressed in Escherichia coli. These proteins were tested in Western blot and ELISA and reactive proteins were also used to identify neutralisation epitopes. VP1 contained serotype specific epitopes whereas VP2 was highly cross-reactive across the serotypes. The C-terminus of VP1 accounted for most of the reactivity of full-length VP1 and was also the location of a neutralising site in each serotype.
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