RESUMEN
Foot and mouth disease (FMD) is a highly contagious infection caused by FMD-virus (FMDV) that affects livestock worldwide with significant economic impact. The main strategy for the control is vaccination with FMDV chemically inactivated with binary ethylenimine (FMDVi). In FMDV infection and vaccination, B cell response plays a major role by providing neutralizing/protective antibodies in animal models and natural hosts. Extracellular vesicles (EVs) and small EVs (sEVs) such as exosomes are important in cellular communication. EVs secreted by antigen-presenting cells (APC) like dendritic cells (DCs) participate in the activation of B and T cells through the presentation of native antigen membrane-associated to B cells or by transferring MHC-peptide complexes to T cells and even complete antigens from DCs. In this study, we demonstrate for the first time that APC activated with the FMDVi O1 Campos vaccine-antigens secrete EVs expressing viral proteins/peptides that could stimulate FMDV-specific immune response. The secretion of EVs-FMDVi is a time-dependent process and can only be isolated within the first 24 h post-activation. These vesicles express classical EVs markers (CD9, CD81, and CD63), along with immunoregulatory molecules (MHC-II and CD86). With an average size of 155 nm, they belong to the category of EVs. Studies conducted in vitro have demonstrated that EVs-FMDVi express antigens that can stimulate a specific B cell response against FMDV, including both marginal zone B cells (MZB) and follicular B cells (FoB). These vesicles can also indirectly or directly affect T cells, indicating that they express both B and T epitopes. Additionally, lymphocyte expansion induced by EVs-FMDVi is greater in splenocytes that have previously encountered viral antigens in vivo. The present study sheds light on the role of EVs derived from APC in regulating the adaptive immunity against FMDV. This novel insight contributes to our current understanding of the immune mechanisms triggered by APC during the antiviral immune response. Furthermore, these findings may have practical implications for the development of new vaccine platforms, providing a rational basis for the design of more effective vaccines against FMDV and other viral diseases.
Asunto(s)
Células Presentadoras de Antígenos , Antígenos Virales , Linfocitos B , Vesículas Extracelulares , Virus de la Fiebre Aftosa , Fiebre Aftosa , Vacunas Virales , Animales , Virus de la Fiebre Aftosa/inmunología , Vesículas Extracelulares/inmunología , Linfocitos B/inmunología , Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Antígenos Virales/inmunología , Vacunas Virales/inmunología , Proteínas Virales/inmunología , Activación de Linfocitos/inmunología , Células Dendríticas/inmunología , Presentación de Antígeno/inmunologíaRESUMEN
This study aims to analyze if the results from different serological assays, used alone or combined, could match the outcome of challenge infection with foot-and-mouth disease virus (FMDV) after vaccination in cattle. Day-of-challenge sera from animals that had been vaccinated 21 days before with monovalent formulations containing inactivated A Iran 96 or A Iran 99 virus strains were used. Challenge and serology were performed with A22 Iraq strain. IgG1 titers and total-IgG avidity indexes were significantly higher in protected animals (p < 0.01) while IgG2-titers were not related to protection (p > 0.05). An IgG1 avidity ELISA was developed to analyze in one step, IgG1 levels and avidity. This assay estimated protection with 96 % accuracy. A strong agreement with challenge results was achieved (K = 0.85), suggesting a role of high-affinity IgG1 in protection against FMDV. These results support the assessment of the single dilution IgG1-Avidity ELISA to predict cross-protection in FMDV-vaccinated cattle.
Asunto(s)
Anticuerpos Antivirales , Afinidad de Anticuerpos , Enfermedades de los Bovinos , Protección Cruzada , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Inmunoglobulina G , Vacunación , Vacunas Virales , Animales , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Bovinos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Virus de la Fiebre Aftosa/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas Virales/inmunología , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/inmunología , Protección Cruzada/inmunología , Vacunación/métodosRESUMEN
Introduction: 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. Therefore, a precise evaluation of the protective capacity of the selected vaccine virus is essential.Areas covered: This article discusses the limitations of currently in use in vitro methods to assess the protective capacity of vaccine strains. It includes the assessment of well-established South American vaccine strains, O1/Campos and A24/Cruzeiro, against outbreaks/emergencies in the continent, as well as against recent isolates from East and Southeast Asia.Expert opinion: In vitro methods, and particularly r1 values, used to evaluate the protective capacity of vaccine strains are not conclusive and do not cover the variety of field scenarios. At present, an option when facing emergencies could be to use well-established vaccine strains with broad antigenic/immunogenic coverage, including conditions that lead to increased coverage such as vaccine formulations and vaccination schemes.
Asunto(s)
Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Vacunas Virales/administración & dosificación , Animales , Protección Cruzada/inmunología , Brotes de Enfermedades/prevención & control , Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/aislamiento & purificación , Serogrupo , Vacunación , Vacunas Virales/inmunologíaRESUMEN
The aim of the present study is to identify the occurrence of abscesses in cattle after the administration of bivalent foot-and-mouth disease vaccine as adverse reaction to components in the new commercial vaccine formulation. Thirty bovines were divided into three groups composed of 10 animals, each. Groups 1 and 2 were vaccinated by researchers based on good vaccination practices criteria. Group 1 was intramuscularly administered with the vaccine, Group 2 received it through subcutaneous route and Group 3 was vaccinated by breeders through subcutaneous route. Animals were selected and observed in vivo in three different moments (7, 28 and 45 days after vaccination). Subsequently, they were observed during post mortem inspection in order to assess the occurrence of vaccine abscesses. Vaccine abscesses were recorded in 40% of bovines in Group 1, in 50% of the ones in Group 2 and in 60% of those in Group 3. There was no significant difference between experimental groups based on the Chi-square test and on Cramer's V analysis; there was no significant difference among experimental groups. Excess of carcass parts presenting vaccine abscesses during post mortem inspection resulted in the meat loss of 1.775 kg in Group 1, of 2.303 kg in Group 2 and of 3.268 kg in Group 3. In conclusion, despite changes in bivalent foot-and-mouth disease vaccine formulation, care should be taken at vaccination time to minimize the occurrence of vaccine abscesses and, consequently, meat losses at slaughter, as well as to reduce losses in beef production chain.(AU)
O presente estudo objetivou identificar a ocorrência de abcessos em bovinos após a aplicação da vacina antiaftosa bivalente, como reação adversa aos componentes da nova formulação comercial. Foram avaliados 30 bovinos divididos em três grupos de 10 animais. Os Grupos 1 e 2 foram vacinados pelos pesquisadores seguindo os critérios de boas práticas de vacinação, sendo o Grupo 1 vacinado pela via intramuscular e o Grupo 2 pela via subcutânea, já o Grupo 3 foi vacinado pelo produtor rural utilizando a via subcutânea. Os animais foram isolados e observados in vivo em três momentos (7°, 28° e 45° dias após a vacinação), em seguida foram observados durante a inspeção post mortem para constatação da ocorrência de abscessos vacinais. Registrou-se a ocorrência de abscessos vacinais em 40% dos bovinos do Grupo 1, em 50% do grupo 2 e em 60% do grupo 3. Não houve diferença significativa entre os grupos experimentais segundo o teste do Qui-quadrado e a análise do V de Cramer. A partes cárneas excisadas das carcaças com abcessos vacinais durante a inspeção post mortem resultaram em uma perda cárnea de 1.775 kg no Grupo 1, de 2.303 kg no Grupo 2 e de 3.268 kg no Grupo 3. Conclui-se, que mesmo com a alteração da formulação da vacina antiaftosa, são necessários cuidados no ato da vacinação, a fim de minimizar a ocorrência de abscessos vacinais e consequentes perdas cárneas no ato do abate dos animais, diminuindo assim os prejuízos à cadeia produtiva da carne.(AU)
Asunto(s)
Animales , Bovinos , Virus de la Fiebre Aftosa/inmunología , Absceso/veterinaria , Vacunas/efectos adversosRESUMEN
Foot-and-mouth disease is a viral illness that affects cloven-hoofed animals causing serious economic losses. Inactivated vaccines against its causative agent, foot-and-mouth disease virus (FMDV), require approximately seven days to induce protection. Therefore, antiviral strategies are needed to provide earlier protection and to stop the spread of this highly contagious virus during outbreak situations. In this way, our group has previously demonstrated that the baculovirus (BV) Autographa californica multiple nucleopolyhedrovirus (AcMNPV), an insect virus with immunostimulant effects, induces a nonspecific antiviral status that protects C57BL/6 mice against a lethal challenge with FMDV A/Arg/01 at 3 hours or 3 days post inoculation. In this work, we studied the immunological mechanisms involved in this protection. Firstly, we compared the protection elicited by AcMNPV in wild type mice and in knock-out mice lacking the subunit IFNAR1 of the receptor for type I interferons (IFNs). Our results showed that type I IFNs are key to prevent the death of the animals after the FMDV challenge. On the other hand, we evaluated the role of NK and NKT cells by depleting these cell subsets with anti-NK1.1 monoclonal antibody. These cells proved to be necessary for the induction of IFN-γ by AcMNPV and to prevent the onset of a severe disease after the FMDV challenge. We propose BV as a novel tool for the development of antiviral strategies because of the high levels of IFNs induced and the NK/NKT cells-mediated immune response elicited.
Asunto(s)
Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Interferón Tipo I/inmunología , Células T Asesinas Naturales/inmunología , Nucleopoliedrovirus/inmunología , Vacunas Virales , Animales , Femenino , Virus de la Fiebre Aftosa/inmunología , Técnicas de Inactivación de Genes , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Receptor de Interferón alfa y beta/genética , Células Sf9 , Spodoptera , Vacunación , Vacunas Virales/inmunologíaRESUMEN
The efficacy of foot-and-mouth disease virus (FMDV) inactivated vaccines is mainly dependent on the integrity of the whole (146S) viral particles. If the intact capsids disassemble to 12S subunits, antibodies against internal-not protective epitopes, may be induced. Serological correlates with protection may be hampered if antibodies against internal epitopes are measured. Here we compared the performance of different ELISAs with the virus-neutralization test (VNT) that measures antibodies against exposed epitopes. Sera from pigs immunized with one dose of an expired commercial FMDV vaccine were used. This vaccine contained about 50% of O1/Campos and over 90% of A24/Cruzeiro strains total antigen as whole 146S particles. Specific-total antibodies were measured with the standard liquid-phase blocking ELISA (LPBE). We also developed an indirect ELISA (IE) using sucrose gradient purified 146S particles as capture antigen to titrate total antibodies, IgM, IgG1 and IgG2. A good correlation was found between VNT titers and IgG-ELISAs for A24/Cruzeiro, with the lowest correlation coefficient estimated for IgG2 titers. For O1/Campos, however, the presence of antibodies against epitopes different from those of the whole capsid, elicited by the presence of 12S particles in the vaccine, hampered the correlation between LPBE and VNT, which was improved by using purified O1/Campos 146S-particles for the liquid-phase of the LPBE. Interestingly, 146S particles but not 12S were efficiently bound to the ELISA plates, confirming the efficiency of the IE to detect antibodies against exposed epitopes. Our results indicate that any serological test assessing total antibodies or IgG1 against epitopes exposed in intact 146S-particles correlate with the levels of serum neutralizing antibodies in vaccinated pigs, and might potentially replace the VNT, upon validation. We recommend that antigen used for serological assays aimed to measure protective antibodies against FMDV should be controlled to ensure the preservation of 146S viral particles.
Asunto(s)
Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/terapia , Enfermedades de los Porcinos/terapia , Porcinos/virología , Vacunas Virales/uso terapéutico , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Fiebre Aftosa/inmunología , Pruebas de Neutralización , Porcinos/inmunología , Enfermedades de los Porcinos/inmunología , Vacunas Virales/inmunologíaRESUMEN
Protection against foot-and-mouth disease virus (FMDV) has been linked to the development of a humoral response. In Argentina, the official control tests for assessing the potency of FMD vaccines are protection against podal generalization (PPG) and expected percentage of protection (EPP) curves built with quantitative data of antibodies determined by liquid-phase blocking ELISA (lpELISA). The results of these tests are used to accept or discard vaccines at the batch level. In this report, a mouse model was assessed as an alternative efficacy control for FMDV vaccines. To this aim, groups of cattle (n = 18) and BALB/c mice (n = 16) were inoculated with commercial FMDV vaccines and bleedings were performed 60 days post vaccination (dpv) in cattle and 21 dpv in mice. Specific FMDV antibody titres were measured in both species by a standardized lpELISA. A statistically significant association between antibody levels in cattle and mice has already been demonstrated. However, some vaccines have been misclassified since they were considered protective based on lpELISA results but did not induce good protection in cattle upon challenge. For this reason, other immunological parameters were evaluated to improve the prediction of protection in mice, without the need of using infective virus. In addition, antibody titres by lpELISA, the IgG2b/IgG1 isotype ratio and the Avidity Index were identified as good predictors, resulting in an optimal predictive model of protection. This mouse model could be a simple and economic alternative for testing FMD vaccines since the disadvantages of high costs and facility requirements associated with the use of large animals are overcome.
Asunto(s)
Anticuerpos Antivirales/inmunología , Enfermedades de los Bovinos/prevención & control , Modelos Animales de Enfermedad , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Inmunoglobulina G/sangre , Vacunas Virales/inmunología , Animales , Argentina , Bovinos , Enfermedades de los Bovinos/virología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Fiebre Aftosa/virología , Masculino , Ratones , Ratones Endogámicos BALB C , Vacunación/veterinariaRESUMEN
Foot-and-mouth disease (FMD) is one of the most contagious veterinary viral diseases known, having economic, social and potentially devastating environmental impacts. The vaccines currently being marketed/sold around the world for disease control and prevention in bovines do not stimulate the production of antibodies having crossed reactions to different serotypes. This means that if an animal becomes infected by a serotype which has not been included in a vaccine then it will develop the disease. Synthetic peptide vaccines represent a safer option and (depending on the design) can stimulate antibodies protecting against different variants. Based on the forgoing, this work was aimed at evaluating FMDV VP1, VP2 and VP3 protein-derived, modified and chemically-synthesised peptides' ability to induce an immune response for developing a vaccine contributing towards controlling the disease. VP1, VP2 and VP3 proteins' conserved regions were selected for this. Peptides from these regions were chemically synthesised; binding assays were then carried out for ascertaining whether they were involved in BHK-21 cell binding. Selected peptides' structure and location were studied. Peptides which did bind were modified and formulated with Montanide ISA 70 adjuvant; 17 animals were immunised twice with the formulation. The animals were genotyped by amplifying the BoLA-DRB3.2 gene. Blood samples were taken from 17 cattle on day 43 post-first immunisation for studying the formulation's immunogenicity. The sera were used in ELISA, immunofluorescence, flow cytometry, immunoadsorption and seroneutralisation assays. The A24 Cruzeiro and O1 Campos virus serotypes were used for these assays. The results revealed that even though protein exposure and 3D structure might be different amongst serotypes, the antibodies so produced could inhibit virus entry to cells, thereby showing the selected peptides' in vitro protection-inducing ability.
Asunto(s)
Virus de la Fiebre Aftosa , Fiebre Aftosa , Péptidos , Vacunas Virales , Animales , Anticuerpos Antivirales , Proteínas de la Cápside/genética , Bovinos , Fiebre Aftosa/prevención & control , Virus de la Fiebre Aftosa/inmunologíaRESUMEN
The aim of the present study is to identify the occurrence of abscesses in cattle after the administration of bivalent foot-and-mouth disease vaccine as adverse reaction to components in the new commercial vaccine formulation. Thirty bovines were divided into three groups composed of 10 animals, each. Groups 1 and 2 were vaccinated by researchers based on good vaccination practices criteria. Group 1 was intramuscularly administered with the vaccine, Group 2 received it through subcutaneous route and Group 3 was vaccinated by breeders through subcutaneous route. Animals were selected and observed in vivo in three different moments (7, 28 and 45 days after vaccination). Subsequently, they were observed during post mortem inspection in order to assess the occurrence of vaccine abscesses. Vaccine abscesses were recorded in 40% of bovines in Group 1, in 50% of the ones in Group 2 and in 60% of those in Group 3. There was no significant difference between experimental groups based on the Chi-square test and on Cramer's V analysis; there was no significant difference among experimental groups. Excess of carcass parts presenting vaccine abscesses during post mortem inspection resulted in the meat loss of 1.775 kg in Group 1, of 2.303 kg in Group 2 and of 3.268 kg in Group 3. In conclusion, despite changes in bivalent foot-and-mouth disease vaccine formulation, care should be taken at vaccination time to minimize the occurrence of vaccine abscesses and, consequently, meat losses at slaughter, as well as to reduce losses in beef production chain.
O presente estudo objetivou identificar a ocorrência de abcessos em bovinos após a aplicação da vacina antiaftosa bivalente, como reação adversa aos componentes da nova formulação comercial. Foram avaliados 30 bovinos divididos em três grupos de 10 animais. Os Grupos 1 e 2 foram vacinados pelos pesquisadores seguindo os critérios de boas práticas de vacinação, sendo o Grupo 1 vacinado pela via intramuscular e o Grupo 2 pela via subcutânea, já o Grupo 3 foi vacinado pelo produtor rural utilizando a via subcutânea. Os animais foram isolados e observados in vivo em três momentos (7°, 28° e 45° dias após a vacinação), em seguida foram observados durante a inspeção post mortem para constatação da ocorrência de abscessos vacinais. Registrou-se a ocorrência de abscessos vacinais em 40% dos bovinos do Grupo 1, em 50% do grupo 2 e em 60% do grupo 3. Não houve diferença significativa entre os grupos experimentais segundo o teste do Qui-quadrado e a análise do V de Cramer. A partes cárneas excisadas das carcaças com abcessos vacinais durante a inspeção post mortem resultaram em uma perda cárnea de 1.775 kg no Grupo 1, de 2.303 kg no Grupo 2 e de 3.268 kg no Grupo 3. Conclui-se, que mesmo com a alteração da formulação da vacina antiaftosa, são necessários cuidados no ato da vacinação, a fim de minimizar a ocorrência de abscessos vacinais e consequentes perdas cárneas no ato do abate dos animais, diminuindo assim os prejuízos à cadeia produtiva da carne.
Asunto(s)
Animales , Bovinos , Absceso/veterinaria , Vacunas/efectos adversos , Virus de la Fiebre Aftosa/inmunologíaRESUMEN
Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which causes severe economic losses in the livestock industry. Currently available vaccines are based on inactivated FMD virus (FMDV). Although inactivated virus vaccines have proved to be effective in FMD control, they have a number of disadvantages, including the need for high bio-containment production facilities and the lack of induction of immunological memory. Novel FMD vaccines based on the use of recombinant empty capsids have shown promising results. These recombinant empty capsids are attractive candidates because they avoid the use of virus in the production facilities but conserve its complete repertoire of conformational epitopes. However, many of these recombinant empty capsids require time-consuming procedures that are difficult to scale up. Achieving production of a novel and efficient FMD vaccine requires not only immunogenic antigens, but also industrially relevant processes. This review intends to summarize and compare the different strategies already published for the production of FMDV recombinant empty capsids, focusing on large-scale production.
Asunto(s)
Proteínas de la Cápside/genética , Fiebre Aftosa/tratamiento farmacológico , Proteínas Recombinantes/genética , Vacunas/genética , Animales , Cápside/química , Cápside/inmunología , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/uso terapéutico , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/efectos de los fármacos , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/patogenicidad , Humanos , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Vacunas/uso terapéutico , Vacunas de Productos Inactivados/genética , Vacunas de Productos Inactivados/inmunologíaRESUMEN
The present study aimed to investigate the kinetics of acute phase proteins and cytokines in the serum of immunized or naive pigs following infection with a field isolate of foot-and-mouth disease (FMD) virus. Five-month-old SPF pigs were intramuscularly immunized with or without the 146S antigen (7.5 µg per head) purified from FMD virus (O/Andong/SKR/2010) and were subsequently challenged 30 days post-vaccination (dpv) with FMD virus on each footpad. Serum samples were obtained at 28 dpv and on days 1, 3, and 5 post-infection (dpi). At 28 dpv, the serum concentrations of C-reactive protein and tumor necrosis factor alpha (TNF-α) were higher in the immunized pigs compared with the non-immunized control pigs. Upon challenge, the levels of all measured acute phase proteins (i.e., C-reactive protein, major acute phase protein, S-amyloid A, and haptoglobin) plateaued at 1 dpi in the immunized pigs whereas they gradually increased up to 5 dpi in the non-immunized control pigs. Levels of serum TNF-α remained higher in the immunized challenged pigs compared with the non-immunized challenged pigs. The serum concentration of interleukin (IL)-6 in the immunized challenged pigs was undetectable at all time points, but moderately increased upon challenge in the non-immunized challenged pigs. IL-1ß was not detected in any of the pigs at any of the observed time points. Collectively, these findings show that the immunized pigs exhibit a rapid serum acute phase protein response following subsequent challenge with the field FMD virus compared with the non-immunized pigs.(AU)
Asunto(s)
Animales , Porcinos/inmunología , Factor de Necrosis Tumoral alfa/análisis , Virus de la Fiebre Aftosa/inmunología , Suero/química , Proteína C-Reactiva/análisis , Proteínas/análisis , Citocinas/análisis , Vacunación/veterinariaRESUMEN
Synthetic peptides mimicking protective B- and T-cell epitopes are good candidates for safer, more effective FMD vaccines. Nevertheless, previous studies of immunization with linear peptides showed that they failed to induce solid protection in cattle. Dendrimeric peptides displaying two or four copies of a peptide corresponding to the B-cell epitope VP1 [136-154] of type O FMDV (O/UKG/11/2001) linked through thioether bonds to a single copy of the T-cell epitope 3A [21-35] (termed B2T and B4T, resp.) afforded protection in vaccinated pigs. In this work, we show that dendrimeric peptides B2T and B4T can elicit specific humoral responses in cattle and confer partial protection against the challenge with a heterologous type O virus (O1/Campos/Bra/58). This protective response correlated with the induction of specific T-cells as well as with an anamnestic antibody response upon virus challenge, as shown by the detection of virus-specific antibody-secreting cells (ASC) in lymphoid tissues distal from the inoculation point.
Asunto(s)
Linfocitos B/inmunología , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/inmunología , Linfocitos T/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Bovinos , Dendrímeros/química , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Activación de Linfocitos , Péptidos/química , Péptidos/inmunología , Porcinos , VacunaciónRESUMEN
In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype spread into most East Asian countries. During 2010-2011 it was responsible for major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine (belonging to the ME-SA topotype) was applied to help control the outbreaks. Subsequently, all susceptible animals were vaccinated every 6â¯months with a vaccine containing the O/Manisa antigen. Despite vaccination, the disease re-occurred in 2014 and afterwards almost annually. This study focuses on the in vivo efficacy in pigs of a high quality monovalent commercial O1/Campos vaccine against heterologous challenge with a representative 2015 isolate from the Jincheon Province of the Republic of Korea. Initially, viral characterizations and r1 determinations were performed on six viruses recovered in that region during 2014-2015, centering on their relationship with the well characterized and widely available O1/Campos vaccine strain. Genetic and antigenic analysis indicated a close similarity among 2014-2015 Korean isolates and with the previous 2010 virus, with distinct differences with the O1/Campos strain. Virus neutralisation tests using O1/Campos cattle and pig post vaccination sera and recent Korean outbreak viruses predicted acceptable cross-protection after a single vaccination, as indicated by r1 values, and in pigs, by expectancy of protection. In agreement with the in vitro estimates, in vivo challenge with a selected field isolate indicated that O1/Campos primo vaccinated pigs were protected, resulting in a PD50 value of nearly 10. The results indicated that good quality oil vaccines containing the O1/Campos strain can successfully be used against isolates belonging to the O Mya98/SEA topotype.
Asunto(s)
Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Inmunización , Enfermedades de los Porcinos/prevención & control , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Línea Celular , Protección Cruzada , Virus de la Fiebre Aftosa/clasificación , Virus de la Fiebre Aftosa/genética , Variación Genética , Filogenia , República de Corea , PorcinosRESUMEN
Foot-and-mouth disease virus (FMDV) causes a highly contagious disease in cloven-hoofed animals. A synthetic vaccine candidate consisting of dendrimeric peptides harbouring two copies of a B-epitope [VP1(136-154)] linked to a T-cell epitope [3A(21-35)] of FMDV confers protection to type O FMDV challenge in pigs. Herein we show in cattle that novel dendrimeric peptides bearing a T-cell epitope [VP1(21-40] and two or four copies of a B-cell epitope [VP1(135-160)] from type O1 Campos FMDV (termed B2T and B4T, respectively) elicited FMDV specific immune responses to similar levels to a commercial vaccine. Animals were challenged with FMDV and 100% of vaccinated cattle with B2T or B4T were protected to podal generalization. Moreover, bovines immunized with B4T were completely protected (with no clinical signs) against FMDV challenge after three vaccine doses, which was associated with titers of viral neutralizing antibodies in serum higher than those of B2T group (p< 0.05) and levels of opsonic antibodies similar to those of animals immunized with one dose of FMDV commercial vaccine. Bovines vaccinated with both dendrimeric peptides presented high levels of IgG1 anti FMDV in sera and in mucosa. When IgA in nasal secretions was measured, 20% or 40% of the animals in B2T or B4T groups respectively, showed anti-FMDV IgA titers. In addition, B2T and B4T peptides evoked similar consistent T cell responses, being recognized in vitro by lymphocytes from most of the immunized cattle in the proliferation assay, and from all animals in the IFN-γ production assay. Taken together, these results support the potential of dendrimers B2T or B4T in cattle as a highly valuable, cost-effective FMDV candidate vaccine with DIVA potential.
Asunto(s)
Dendrímeros/farmacología , Fiebre Aftosa/prevención & control , Péptidos/farmacología , Animales , Bovinos , Virus de la Fiebre Aftosa/inmunología , Porcinos , Vacunas ViralesRESUMEN
Galectin-8 (Gal-8) is a mammalian ß-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs). Proinflammatory cytokines IL-3, IL-2, IL-6, TNF, MCP-1, and MCP-5, as well as growth factor G-CSF, were augmented in Gal-8-BMDC conditioned media, with IL-6 as the most prominent. Remarkably, BMDCs from Gal-8-deficient mice (Lgals8-/- BMDC) displayed reduced CD86 and IL-6 expression and an impaired ability to promote antigen-specific CD4 T cell activation. To test if Gal-8-induced activation correlates with the elicitation of an effective immune response, soluble Gal-8 was coadministrated with antigen during immunization of BALB/cJ mice in the experimental foot-and-mouth disease virus (FMDV) model. When a single dose of Gal-8 was added to the antigen formulation, an increased specific and neutralizing humoral response was developed, sufficient to enhance animal protection upon viral challenge. IL-6 and IFN-γ, as well as lymphoproliferative responses, were also incremented in Gal-8/antigen-immunized animals only at 48 h after immunization, suggesting that Gal-8 induces the elicitation of an inflammatory response at an early stage. Taking together, these findings argue in favor of the use of Gal-8 as an immune-stimulator molecule to enhance the adaptive immune response.
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Presentación de Antígeno , Antígenos Virales/inmunología , Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Fiebre Aftosa/inmunología , Galectinas/inmunología , Inmunidad Adaptativa , Animales , Antígenos Virales/administración & dosificación , Antígenos Virales/genética , Linfocitos T CD4-Positivos/virología , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Células Dendríticas/virología , Fiebre Aftosa/genética , Fiebre Aftosa/prevención & control , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/crecimiento & desarrollo , Virus de la Fiebre Aftosa/inmunología , Galectinas/genética , Galectinas/farmacología , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos/genética , Factor Estimulante de Colonias de Granulocitos/inmunología , Inmunización , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-3/genética , Interleucina-3/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Quimioatrayentes de Monocitos/genética , Proteínas Quimioatrayentes de Monocitos/inmunología , Transducción de Señal , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Identifying vaccine strains to control outbreaks of foot-and-mouth disease virus that could spread to new regions is essential for contingency plans. This is the first report on the antigenic/immunogenic relationships of the South American O1/Campos vaccine strain with representative isolates of the three currently active Asian type O topotypes. Virus neutralization tests using O1/Campos post-vaccination sera derived from cattle and pigs predicted for both species acceptable cross-protection, even after single vaccination, established by r1 values and by expectancy of protection using monovalent or polyvalent vaccines. The results indicate that effective oil vaccines containing the O1/Campos strain can be used against Asian isolates, expanding the scope of O1/Campos strain included in vaccine banks to control emergencies caused by Asian viruses, even on single-dose vaccination, and to cover the need of effective vaccines in Asia during systematic vaccination.
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Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Vacunas Virales/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/sangre , Protección Cruzada , Reacciones Cruzadas , Ratones , Pruebas de NeutralizaciónRESUMEN
BACKGROUND: Bovine Leukemia Virus (BLV) produces disorders on the immune system in naturally infected animals, which may counteract the development of immunity after vaccination. The aim of this study was to investigate whether healthy and BLV infected cattle elicited similar humoral responses after foot and mouth disease (FMD) immunization. In a field study, 35 Holstein heifers were selected based on their BLV serological status and immunized with a single dose of a commercial bivalent oil-based FMD vaccine. Serum samples were collected at 0, 15, 60, 165 and 300 days post vaccination (dpv). RESULTS: Total anti-A24/Cruzeiro antibodies, IgM, IgG1, IgG2 titers and avidity index of specific antibodies were determined by ELISA. Although only marginally significant differences were found between groups in terms of total antibodies, anti-FMD IgM and IgG1 titers were significantly lower in heifers infected with BLV at the 15 dpv (p < 0.01). Animals that became infected during the study did not show differences to the BLV negative group. CONCLUSIONS: Cattle infected with BLV at the time of immunization may elicit a low-magnitude serological response to a commercial Foot-and-mouth disease vaccine.
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Enfermedades de los Bovinos/inmunología , Leucosis Bovina Enzoótica/inmunología , Virus de la Fiebre Aftosa/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Bovinos , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/virología , Leucosis Bovina Enzoótica/virología , Femenino , Virus de la Leucemia Bovina , Vacunas de Productos Inactivados/inmunologíaRESUMEN
A large number of Brazilian zoos keep many endangered species of deer, however, very few disease surveillance studies have been conducted among captive cervids. Blood samples from 32 Brazilian deer (Blastocerus dichotomus, Mazama nana and Mazama americana) kept in captivity at Bela Vista Biological Sanctuary (Foz do Iguaçu, Brazil) were investigated for 10 ruminant pathogens, with the aims of monitoring deer health status and evaluating any potential zoonotic risk. Deer serum samples were tested for Brucella abortus, Leptospira (23 serovars), Toxoplasma gondii, Neospora caninum, bovine viral diarrhea virus, infectious bovine rhinotracheitis virus, foot-and-mouth disease virus, western equine encephalitis virus, eastern equine encephalitis virus and Venezuelan equine encephalitis virus. Antibodies against T. gondii (15.6%), N. caninum (6.2%) and L. interrogans serogroup Serjoe (3.1%) were detected. The serological results for all other infectious agents were negative. The deer were considered to be clinically healthy and asymptomatic regarding any disease. Compared with studies on free-ranging deer, the prevalences of the same agents tested among the captive deer kept at the Sanctuary were lower, thus indicating good sanitary conditions and high-quality management practices at the zoo.
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Animales de Zoológico/inmunología , Anticuerpos Antiprotozoarios/sangre , Ciervos/inmunología , Leptospira interrogans/inmunología , Neospora/inmunología , Toxoplasma/inmunología , Animales , Brasil/epidemiología , Brucella abortus/inmunología , Coccidiosis/epidemiología , Virus de la Diarrea Viral Bovina/inmunología , Virus de la Encefalitis/inmunología , Virus de la Fiebre Aftosa/inmunología , Herpesvirus Bovino 1/inmunología , Estudios Seroepidemiológicos , Toxoplasmosis Animal/epidemiologíaRESUMEN
Abstract A large number of Brazilian zoos keep many endangered species of deer, however, very few disease surveillance studies have been conducted among captive cervids. Blood samples from 32 Brazilian deer (Blastocerus dichotomus, Mazama nana and Mazama americana) kept in captivity at Bela Vista Biological Sanctuary (Foz do Iguaçu, Brazil) were investigated for 10 ruminant pathogens, with the aims of monitoring deer health status and evaluating any potential zoonotic risk. Deer serum samples were tested for Brucella abortus, Leptospira (23 serovars), Toxoplasma gondii, Neospora caninum, bovine viral diarrhea virus, infectious bovine rhinotracheitis virus, foot-and-mouth disease virus, western equine encephalitis virus, eastern equine encephalitis virus and Venezuelan equine encephalitis virus. Antibodies against T. gondii (15.6%), N. caninum (6.2%) and L. interrogans serogroup Serjoe (3.1%) were detected. The serological results for all other infectious agents were negative. The deer were considered to be clinically healthy and asymptomatic regarding any disease. Compared with studies on free-ranging deer, the prevalences of the same agents tested among the captive deer kept at the Sanctuary were lower, thus indicating good sanitary conditions and high-quality management practices at the zoo.
Resumo Um grande número de zoológicos brasileiros abriga espécies de cervídeos ameaçados de extinção, entretanto, estudos de vigilância de doenças em cervídeos de cativeiro são escassos. Amostras de sangue de 32 cervídeos brasileiros (Blastocerus dichotomus, Mazama nana e Mazama americana), mantidos em cativeiro no Refúgio Biológico Bela Vista (Foz do Iguaçu, Brasil), foram investigados para 10 patógenos de ruminantes, visando monitorar o estado de saúde dos cervídeos e avaliar a presença de agentes zoonóticos. As amostras de soro foram testadas para Brucella abortus, Leptospira (23 sorovares), Toxoplasma gondii, Neospora caninum, diarreia viral bovina, rinotraqueíte infecciosa bovina, febre aftosa, encefalomielite equina do oeste, encefalomielite equina do leste e encefalomielite equina venezuelana. Foram detectados anticorpos para T. gondii (15,6%), N. caninum (6,2%) e para L. interrogans sorogrupo Serjoe (3,1%). As sorologias apresentaram resultado negativo para as demais doenças. Os cervídeos foram considerados clinicamente sadios e assintomáticos para doenças. Comparados aos estudos de populações de vida livre, as soroprevalências para os mesmos agentes testados foram menores para os cervídeos mantidos no Refúgio, indicando as boas condições sanitárias e a qualidade das práticas de manejo no zoológico.
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Animales , Toxoplasma/inmunología , Ciervos/inmunología , Anticuerpos Antiprotozoarios/sangre , Neospora/inmunología , Leptospira interrogans/inmunología , Animales de Zoológico/inmunología , Brasil/epidemiología , Brucella abortus/inmunología , Estudios Seroepidemiológicos , Toxoplasmosis Animal/epidemiología , Coccidiosis/epidemiología , Virus de la Diarrea Viral Bovina/inmunología , Herpesvirus Bovino 1/inmunología , Virus de la Fiebre Aftosa/inmunología , Virus de la Encefalitis/inmunologíaRESUMEN
Foot and mouth disease is caused by a non-enveloped virus (FMDV), which disposes several antigenic sites at the surface of their capsid proteins. The most relevant and immunodominant antigenic site of FMDV (site A or AnSA) includes a key virus-cell interaction element (RGD motif) located in the Viral Protein 1 (VP1), more precisely at the GH loop. AnSA includes a set of overlapped and mainly linear epitopes, which are the main targets of the humoral immune response. Taking advantage over specific structural features of the GH loop, we have evaluated the influence of every amino acid residue at AnSA in the interaction with 2 neutralizing antibodies by molecular modeling techniques. Additionally, we constructed diverse interaction complexes with multiple site A mutants and discussed about the structural influence of amino acidic insertions in such relevant antigenic site of FMDV. Our approach is in agreement with previous ELISA experiments and allows the understanding of how FMDV mutations may alter the interaction with different antibodies, as we can estimate the contribution of each amino acid to the interaction. Overall, our work contributes to the development of specific vaccination strategies for FMD control.