FMD vaccine matching: Inter laboratory study for improved understanding of r1 values

Foot-and-mouth disease virus (FMDV) is a highly variable RNA virus existing as seven different serotypes. The antigenic variability between and within serotypes can limit the cross-reactivity and therefore the in vivo cross-protection of vaccines. Selection of appropriate vaccine strains is crucial in the control of FMD. Determination of indirect relationships (r1-value) between potential vaccine strains and field strains based on antibody responses against both are routinely used for vaccine matching purposes. Aiming at the investigation of the repeatability, reproducibility and comparability of r1-value determination within and between laboratories and serological tests, a small scale vaccine matching ring test for FMDV serotype A was organized. Well-characterized serum pools from cattle vaccinated with a monovalent A24/Cruzeiro/Brazil/55 (A24) FMD vaccine with known in vivo protection status (homologous and heterologous) were distributed to four laboratories to determine r1-values for the heterologous FMD strains A81/Argentina/87, A/Argentina/2000 and A/Argentina/2001 using the virus neutralization tests (VNT) and liquid phase blocking ELISA (LPBE). Within laboratories, the repeatability of r1-value determination was high for both antibody assays. VNT resulted in reproducible and comparable r1-values between laboratories, indicative of a lack of antigenic relatedness between the A24 strain and the heterologous strains tested in this work, thus corresponding to some of the in vivo findings with these strains. Using LPBE, similar trends in r1-values were observed in all laboratories, but the overall reproducibility was lower than with VNT. Inconsistencies between laboratories may at least in part be attributed to differences in LPBE protocols as well as the in preexisting information generated in each laboratory (such as antibody titer-protection correlation curves). To gain more insight in the LPBE-derived r1-values standard bovine control sera were included in the antibody assays performed in each laboratory and a standardization exercise was performed.Fil: Willems, Tom. No especifíca;Fil: De Vleeschauwer, Annebel. No especifíca;Fil: Pérez Filgueira, Daniel Mariano. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Virologia E Innovaciones Tecnologicas. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Virologia E Innovaciones Tecnologicas.; ArgentinaFil: Li, Yanmin. No especifíca;Fil: Ludi, Anna. No especifíca;Fil: Lefebvre, David. No especifíca;Fil: Wilsden, Ginette. No especifíca;Fil: Statham, Bob. No especifíca;Fil: Haas, Bernd. Federal Research Institute for Animal Health; AlemaniaFil: Mattion, Nora Marta. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Robiolo, Blanca. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Beascoechea Perez, Claudia. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Smitsaart, Eliana. Biogénesis Bagó; ArgentinaFil: la Torre, Jose Leonardo. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: De Clercq, Kris. No especifíca

Phylogeographic analysis of the 2000-2002 foot-and-mouth disease epidemic in Argentina

Foot-and-mouth disease (FMD) is a highly transmissible disease of hooved livestock. Although FMD has been eradicated from many countries, economic and social consequences of FMD reintroductions are devastating. After achieving disease eradication, Argentina was affected by a major epidemic in 2000-2002, and within few months, FMD virus spread throughout most of the country and affected >2500 herds. Available records and viral strains allowed us to assess the origins, spread and progression of this FMD epidemic, which remained uncertain. We used whole genome viral sequences and a continuous phylogeographic diffusion approach, which revealed that the viruses that caused the outbreaks spread fast in different directions from a central area in Argentina. The analysis also suggests that the virus that caused the outbreaks in the year 2000 was different from those found during the 2001 epidemic. To estimate if the approximate overall genetic diversity of the virus was related to disease transmission, we reconstructed the viral demographic variation in time using Bayesian Skygrid approach and compared it with the epidemic curve and the within-herd transmission rate and showed that the genetic temporal diversity of the virus was associated with the increasing number of outbreaks in the exponential phase of the epidemic. Results here provide new evidence of how the disease entered and spread throughout the country. We further demonstrate that genetic data collected during a FMD epidemic can be informative indicators of the progression of an ongoing epidemicInst. de BiotecnologíaFil: Brito, Barbara. USDA/ARS Foreign Animal Disease Research Unit, Plum Island Animal Disease Center; Estados UnidosFil: Konig, Guido Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Cabanne, Gustavo Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Perez Beascoechea, Claudia. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Dirección de Laboratorio Animal, ArgentinaFil: Rodriguez, Luis. USDA/ARS Foreign Animal Disease Research Unit, Plum Island Animal Disease Center; Estados UnidosFil: Perez, Andres. University of Minnesota. College of Veterinary Medicine. Department of Veterinary Population Medicine; Argentin

Protective effects of high-potency FMDV O₁ Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination

Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21. days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7. days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7. days prior to challenge, but was not protective with just 4. days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7. days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures

Confidence in indirect assessment of foot-and-mouth disease vaccine potency and vaccine matching carried out by liquid phase ELISA and virus neutralization tests

The necessity of avoiding the use of animals in vaccine potency testing has been widely recognized. The repeatability and reproducibility of the Expected Percentage of Protection (EPP) as a serological potency surrogate for A24 Cruzeiro foot-and-mouth disease virus (FMDV) strain was assessed, and compared with the results obtained with challenge in the Protection against Podal Generalization (PPG) test. To determine the EPPs, the serum titers obtained by liquid phase blocking competitive ELISA (lpELISA) and virus neutralization (VNT) in 10 potency trials using the same A24 Cruzeiro vaccine, were interpolated into previously validated logit transformation curves that correlate PPG with serology. Indirect serological assessment of vaccine matching between the serotype A FMDV strains A24 Cruzeiro and A/Argentina/01 was also carried out by lpELISA and VNT. The results obtained in this study strongly support the replacement of challenge tests for vaccine potency by indirect serological assays, at least for A24 Cruzeiro FMDV strain. While determination of EPPs by lpELISA titers showed an excellent repeatability, reproducibility and concordance with PPG for vaccine potency, assessments of cross-protection by VNT titers were more consistent with the PPG outcome.Fil: Robiolo, Blanca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: la Torre, Jose Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Beascoechea, Claudia Perez. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Perez, Alejandro. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Seki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Smitsaart, Eliana. Biogénesis-Bagó S.A.; ArgentinaFil: Fondevila, Norberto Antonio. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas; ArgentinaFil: Palma, Eduardo Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas; ArgentinaFil: Goris, Nesya. Veterinary and Agrochemical Research Centre; BélgicaFil: De Clercq, Kris. Veterinary and Agrochemical Research Centre; BélgicaFil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentin

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. A monovalent vaccine formulated with the representative 2010 strain elicited high antibody titers and protected against challenge with homologous virus. In addition, cross-reactive antibodies to predominant viruses in the region were established. In overall this study indicates the ability of the virus to diversify under field conditions in which a vaccine strain with poor match is applied, and the potential of the selected 2010 field virus as a vaccine candidate for incorporation into strategic antigen banks and/or for addition to current formulations for systematic vaccination, in order to prevent the emergence of even more divergent isolates in the future.Fil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Perez Beascoechea, Claudia. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Espinoza, Ana Maria. Biogénesis Bagó; ArgentinaFil: Galdo Novo, Sabrina. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Smitsaart, Eliana. Biogénesis Bagó; ArgentinaFil: Salgado, Gustavo. Instituto de Medicina e Higiene Tropical “Izquieta Perez”; EcuadorFil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Rodríguez Toledo, Jorge. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentin

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. The high level of sequence conservation among different isolates in the various regions of Ecuador pointed to a common origin, suggesting animal movements as possible sources of viral spread. Monoclonal antibody profiling grouped the isolates in two major reactivity patterns which differed from that of the vaccine strain. Both profiles showed loss of reactivity with the same four MAbs, three of them with neutralizing properties. Additional sites were lost in the profile representing most of the 2010s viral samples. Levels of protective antibodies induced by the vaccine against the field strains assessed by in vitro vaccine matching studies also pointed to an increased temporal pattern of loss of a protective response. Moreover, results obtained with in vivo challenge in the protection against podal generalization test in cattle, clearly indicated lack of appropriate protection of the Ecuadorian field strains by the vaccine virus in use, which in the case of a 2010 variant was observed even after revaccination.Fil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Perez Beascoechea, Claudia. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Salgado, Gustavo. Instituto de Medicina e Higiene Tropical “Izquieta Perez”; PerúFil: Seki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Pedemonte, Andrea. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Bonastre, Paula. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: D'Aloia, Ricardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: la Torre, Jose Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Rodríguez Toledo, Jorge. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentin

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 VP1 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 O1/Campos, including the loss of reactivity with neutralizing MAbs, were recognized. Levels of protective antibodies induced by the vaccine containing the O1/ Campos strain against the San Pedro virus and the virus responsible for the previous emergency in 2006 in the Southern Cone assessed by in vitro vaccine matching studies pointed to an insufficient protective response 30 days after vaccination (DPV), which was properly attained at 79 DPV or after revaccination. In agreement with the in vitro assessment, the in vivo challenge in the Protection against Podal Generalization test in cattle indicated appropriate protection for the San Pedro strain at 79 DPV or after revaccination. The complementary conclusions that can be derived from vaccine matching tests designed differently to fit the various objectives intended: prophylaxis, emergency vaccination or incorporation of new field strains into antigen banks, is evaluated. This is the first report of the antigenic and immunogenic characterization of the variants responsible for emergencies in the Southern Cone of South America and the putative impact of the changes on the cross protection conferred by the vaccine strain.Fil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;Fil: Perez Beascoechea, Claudia. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: Oviedo Benitez, Elizabeth. Servicio Nacional de Calidad y Salud Animal; Paraguay;Fil: Pedemonte, Andrea. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: Seki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;Fil: Galdo Novo, Sabrina. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: Balette, Cristina. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: D'aloia, Ricardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: la Torre, Jose Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;Fil: Mattion, Nora Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología;Fil: Rodriguez Toledo, Jorge. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina;Fil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología