Why Foot-and-Mouth Disease-Free with Vaccination Should Be Equivalent to Foot-and-Mouth Disease-Free without Vaccination.

Foot-and-Mouth Disease (FMD) is still one of the most relevant animal diseases and remains of global concern. The World Organization for Animal Health (WOAH) has specified two sanitary statuses that assure freedom from FMD: a country or zone can be free from FMD either with or without vaccination. To obtain either of the two statuses, absence of virus circulation must be shown.

Broad immunogenic spectrum of monovalent and trivalent foot-and-mouth disease virus vaccines containing O campos, A24 cruzeiro and A Argentina 2001 strains against circulating viral lineages in cattle and pigs.

FMD remains endemic in many Asian and African countries where multiple variants of serotypes O and A, among others, currently circulate. Due to lack of cross-protection between serotypes and incomplete protection between some strains even within a serotype, an important challenge for the application of effective vaccination programs is to select highly immunogenic and widely cross-reactive vaccine strains. Adaptation of a candidate field virus for use as a vaccine can be quite complex, so that whenever possible, the use of well-established vaccine viruses could have enormous advantages.

Expression of recombinant dengue virus type 1 non-structural protein 1 in mammalian cells and preliminary assessment of its suitability to detect human IgG antibodies elicited by viral infection.

In recent years dengue has become a rapidly growing public health problem worldwide, however, the availability of accurate and affordable diagnostic immunoassays is limited, partly due to the difficulty of producing large quantities of purified antigen. Non-structural protein 1 (NS1) has shown to be a good candidate for inclusion in diagnostic assays and for serosurveys, particularly in endemic countries as a prerequisite for vaccination. In this work the NS1 antigen derived from dengue virus type-1 (DENV1) was expressed in HEK293-T cells and purified by affinity chromatography.

Challenges in foot-and-mouth disease virus strain selection as an input to attain broad vaccine intraserotype cross-protection.

: Vaccination against foot-and-mouth disease virus is regarded as the most effective way to prevent disease. Selection of appropriate vaccine strains is challenging due to lack of cross-protection between serotypes and incomplete protection between some strains within a serotype. Vaccine effectiveness can be affected by vaccine formulation, vaccination approaches, and also by emerging field variants.

Recombinant foot-and-mouth disease virus (FMDV) non-structural protein 3A fused to enhanced green fluorescent protein (EGFP) as a candidate probe to identify FMDV-infected cattle in serosurveys.

Recombinant protein 3A-EGFP, a fusion construct between foot-and-mouth disease virus (FMDV) non-structural protein 3A and the enhanced green fluorescent protein (EGFP) was expressed in BL21-DE3 cells. The identity of the partially purified protein 3A-EGFP was confirmed by its reactivity with sera from cattle infected with FMDV and with a monoclonal antibody specific for FMDV-3ABC (MAb3H7) in Western blot assays. No reactivity was observed with sera from uninfected vaccinated animals.

Redefining the "carrier" state for foot-and-mouth disease from the dynamics of virus persistence in endemically affected cattle populations.

The foot-and-mouth disease virus (FMDV) "carrier" state was defined by van Bekkum in 1959. It was based on the recovery of infectious virus 28 days or more post infection and has been a useful construct for experimental studies. Using historic data from 1,107 cattle, collected as part of a population based study of endemic FMD in 2000, we developed a mixed effects logistic regression model to predict the probability of recovering viable FMDV by probang and culture, conditional on the animal's age and time since last reported outbreak.

Emergence of antigenic variants of Foot-and-Mouth Disease Virus serotype O in Ecuador and preliminary evaluation of a field strain as a vaccine candidate.

Foot-and-Mouth Disease Virus serotype O has been circulating regularly throughout most provinces of Ecuador, one of the two South American countries that still remain endemic, although satisfactory vaccination coverage was reported. This study concentrates in the characterization of isolates collected during 2008-2011, focusing particularly on the antigenic and immunogenic relationships of the field viruses with the O1/Campos vaccine strain in use in the region and with an experimental vaccine formulated with a representative strain of the 2010 epidemic. The results established that antigenically divergent variants poorly protected by the vaccine in use emerged and co-circulated in a limited period of time.

Characterization of a type O foot-and-mouth disease virus re-emerging in the year 2011 in free areas of the Southern Cone of South America and cross-protection studies with the vaccine strain in use in the region.

Molecular, antigenic and vaccine matching studies, including protective response in vivo, were conducted with a foot-and-mouth disease type O virus isolated during the outbreak in September 2011 in San Pedro, Paraguay, country internationally recognized as free with vaccination in 1997. The phylogenetic tree derived from complete VP(1) sequences as well as monoclonal antibody profiling indicated that this isolate was related to viruses responsible for previous emergencies in free areas of the Southern Cone of South America occurring sporadically between the years 2000 and 2006. Marked differences with the vaccine strain O(1)/Campos, including the loss of reactivity with neutralizing MAbs, were recognized.

Molecular epidemiology of foot-and-mouth disease virus type A in South America.

A databank of 78 VP(1) complete sequences of type A foot-and-mouth disease virus (FMDV) from South American isolates was constructed. Forty-nine samples corresponded to FMDV that circulated between the years 1999-2008, mainly in Venezuela, where most type A outbreaks have occurred lately and twenty-nine to strains historically relevant for the continent. The phylogenetic analysis showed that all South American FMDV belonged to the Euro-SA topotype.

Characterization of foot-and-mouth disease virus from outbreaks in Ecuador during 2009-2010 and cross-protection studies with the vaccine strain in use in the region.

During the years 2009 and 2010 relevant epidemic waves of foot-and-mouth disease (FMD) serotype O occurred in Ecuador, representing a great drawback for the last stages of the ongoing eradication program in South America. This study describes the molecular and antigenic characterizations of 29 isolates collected from various regions in the country and their relationship to the vaccine strain. The phylogenetic tree derived from sequences spanning the complete VP(1) protein showed that, despite the widespread origin of the viruses, they were all related among themselves and to previous isolates occurring in 2008, with around 10% difference with the vaccine strain O1/Campos.

Phylogenetic analysis of Foot-and-Mouth Disease Virus type O circulating in the Andean region of South America during 2002-2008.

At present, Foot-and-Mouth Disease (FMD) has been successfully controlled in most territories of South America, where only Ecuador and Venezuela remain as endemic countries. In this context, the precise characterization of circulating viruses is of utmost importance. This work describes the first molecular epidemiology study performed with the complete VP(1)-coding region of 114 field isolates of FMD virus (FMDV) type O, collected in the Andean countries mainly during 2002-2008.

Use of continuous results to compare ELISAs for the detection of antibodies to non-structural proteins of foot-and-mouth disease virus.

Six tests for detection of antibodies against the non-structural proteins of foot-and-mouth disease virus (FMDV) were compared at an international workshop in Brescia, Italy in 2004 on the basis of dichotomous test results. However, as results from all of these assays were also available on a continuous scale, validation was extended by calculating and subsequently analysing the receiver-operator characteristic (ROC) curves and likelihood ratios (LR) for each test method. For the purposes of these analyses, test results for a total of 1337 sera were selected from the Brescia workshop dataset, 237 sera that had been obtained from cattle exposed to FMDV and 1100 sera obtained from cattle that were not exposed to the virus; sera from "exposed" cattle were considered to be "true positives" and sera from "non-exposed" cattle were considered to be "true negatives".

Genetic variation of foot-and-mouth disease virus isolates recovered from persistently infected water buffalo (Bubalus bubalis).

Genetic variation of foot-and-mouth disease virus (FMDV) isolates, serotype O, recovered serially over a 1-year period from persistently infected buffalos was assessed. The persistent state was established experimentally with plaque-purified FMDV, strain O(1)Campos, in five buffalos (Bubalus bubalis). Viral isolates collected from esophageal-pharyngeal (EP) fluids for up to 71 weeks after infection were analyzed at different times by nucleotide sequencing and T(1) RNase oligonucleotide fingerprinting to assess variability in the VP1-coding region and in the complete genome, respectively.

Phylogenetic analysis of foot-and-mouth disease virus type O re-emerging in free areas of South America.

The nucleotide sequences of the complete VP(1)-coding region of foot-and-mouth disease viruses (FMDV), type O, isolated during the recent emergencies of the disease in free areas of South America (Mato Grosso do Sul, Brazil, October 2005, and Corrientes, Argentina, February 2006), were determined. Also established were the complete VP(1)-coding sequences of viruses occurring in neighbouring locations between the years 2000 and 2003. A phylogenetic analysis was performed based on comparison with continental relevant field and vaccine strains, as well as with extra-continental representative viruses.

Evaluation of three 3ABC ELISAs for foot-and-mouth disease non-structural antibodies using latent class analysis.

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease of even-toed ungulates. Serological diagnosis/surveillance of FMD presents several problems as there are seven serotypes worldwide and in the event of vaccination it may be necessary to be able to identify FMD infected/exposed animals irrespective of their vaccination status. The recent development of non-structural 3ABC protein (NSP) ELISA tests has greatly advanced sero-diagnosis/surveillance as these tests detect exposure to live virus for any of the seven serotypes of FMD, even in vaccinated populations.

Application of non-structural protein antibody tests in substantiating freedom from foot-and-mouth disease virus infection after emergency vaccination of cattle.

There has been much debate about the use of the so-called "vaccinate-to-live" policy for the control of foot-and-mouth disease (FMD) in Europe, according to which, spread of the FMD virus (FMDV) from future outbreaks could be controlled by a short period of "emergency" vaccination of surrounding herds, reducing the need for large-scale preemptive culling of at-risk animals. Since vaccinated animals may become subclinically infected with FMDV following challenge exposure, it is necessary to either remove all vaccinates (vaccinate-to-kill) or to detect and remove vaccinates in which virus is circulating or has established persistent infections (vaccinate-to-live), in order to rapidly regain the most favoured trading status of FMD-free without vaccination. The latter approach can be supported by testing vaccinated animals for the presence of antibodies to certain non-structural proteins (NSP) of FMDV, which are induced by infection with the virus, but not by vaccination with purified FMD vaccines.

Evolving perception on the benefits of vaccination as a foot and mouth disease control policy: contributions of South America.

Within the past decade, changes in perceptions on the benefits of vaccination as an appropriate tool to achieve complete foot and mouth disease eradication have become evident. The former negative view was derived from misconceptions, resulting mainly from the belief that vaccines are not entirely effective and that vaccination masks asymptomatic viral circulation. The advent in the 1990s of vaccination policies implemented within a strategic eradication plan in South America, and during recurrence of the disease in disease-free regions contributed towards generating more reliable and visible outcomes of vaccination programs, paving the way towards a new perception.