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1.
Virol J ; 21(1): 250, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39375730

RESUMEN

The research was conducted in Jimma town, Oromiya Regional State, from October 2022 to June 2023, with the aim of assessing the immune response of polyvalent FMD (Foot and Mouth Disease) vaccine. The study involved 34 cattle in a longitudinal study, divided into two groups: 29 vaccinated and 5 unvaccinated. The vaccinated cattle received an inactivated polyvalent FMD virus vaccine produced by the National Veterinary Institute. Blood samples were collected on days 0, 14, 21, 35, 80, and 125 after vaccination and tested using Virus Neutralization Test and 3ABC ELISA. The results showed a significant increase in neutralizing antibodies against structural proteins in all vaccinated cattle on day 14 after vaccination for all three serotypes. (A/ETH/21/2000, p = 0.015; O/ETH/38/2005, p = 0.017; SAT2/ETH/64/2009, p = 0.007). On day, fourteen of post-vaccination vaccinated group showed immune response equal or above 1.5 log10 in a proportion of 69%, 73% and 94% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The status of raised antibody titer on day 125 post-vaccination showed decreasing by 14%, 18% and 4% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The DIVA test, or 3ABC ELISA, used to differentiate infected from vaccinated animals, revealed the absence of immune response to the Non-structural protein in the vaccinated cattle group. Conversely, the unvaccinated group showed no recorded antibody titer to both structural and non-structural proteins. In summary, the commercially available FMD vaccine, comprising serotype A, O, and SAT2, triggers an immune response to the structural protein rather than the non-structural protein after the initial administration. This outcome implies that FMD vaccines from the National Veterinary Institute align with the DIVA test. Nevertheless, additional efforts may be necessary to bolster the strength and duration of the vaccine-induced immune response.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Enfermedades de los Bovinos , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Pruebas de Neutralización , Vacunas de Productos Inactivados , Vacunas Virales , Animales , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Bovinos , Anticuerpos Antivirales/sangre , Virus de la Fiebre Aftosa/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Anticuerpos Neutralizantes/sangre , Etiopía , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Estudios Longitudinales , Serogrupo , Vacunación
2.
Nat Commun ; 15(1): 8774, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39389971

RESUMEN

Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Antígenos Virales , Virus de la Fiebre Aftosa , Fiebre Aftosa , Virus de la Fiebre Aftosa/inmunología , Animales , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Fiebre Aftosa/virología , Porcinos , Antígenos Virales/inmunología , Antígenos Virales/química , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/química , Epítopos/inmunología , Epítopos/química , Virión/inmunología , Virión/ultraestructura , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Vacunas Virales/inmunología , Cápside/inmunología , Cápside/ultraestructura , Cápside/química , Modelos Moleculares
3.
Sci Rep ; 14(1): 23958, 2024 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-39397089

RESUMEN

ELISA kits that detect antibodies to the non-structural protein (NSP) of the foot-and-mouth disease virus (FMDV), commonly referred to as NSP-ELISA, can distinguish between vaccinated and naturally infected animals. They can play an essential role in demonstrating 'proof-of-freedom' during the control of FMD. Although various NSP-ELISA kits are available in Thailand, information regarding their performance is lacking. To select the most appropriate NSP-ELISA kit for our specific purpose, we must compare their performance using carefully characterized sera. This will ensure that we maximize the benefits of our testing. In this study, six NSP-ELISA kits sold in Thailand-Biovet, ID Screen, VDPro, IDEXX, PrioCHECK, and KUcheck-F-were evaluated and compared. A total of 800 serum samples were examined, including samples from 357 cattle and 29 buffaloes in outbreak areas, as well as 14 swine serum samples from the Vaccine Quality Control Unit of the Bureau of Veterinary Biologics, Ministry of Agriculture and Cooperation, Thailand. Four hundred samples were confirmed to originate from animals infected with FMDV through ELISA typing (n = 11, tested as representative samples in each farm) and/or RT-PCR (n = 400, all samples), serving as positive control sera. Additionally, 400 negative control sera were obtained from Japan (97 cattle and 300 pigs) and Australia (3 goats), certified by the World Organisation for Animal Health as 'free of FMD'. The sensitivity and specificity of the six tests were determined based on the results obtained from two-by-two tables. Cohen's kappa statistics were calculated for the six tests to assess their concordance, and the diagnostic accuracy of the assays was also determined. For all six NSP-ELISA kits, the sensitivity ranged from 97.75 to 99.50%, and the specificity ranged from 97.25 to 100%. Cohen's kappa statistics ranged from 0.96 to 1.00, and diagnostic accuracy ranged from 98.13 to 99.75%. The study results indicated that the test kits have statistically similar sensitivity, specificity, concordance, and diagnostic accuracy, suggesting they can be used interchangeably. However, ID Screen demonstrated the highest sensitivity and specificity among all kits tested. Therefore, if a single kit were to be selected from the six evaluated, ID Screen would be the most appropriate choice. These findings can aid in selecting the most suitable test kit. Therefore, it is recommended to consider purchasing a diverse range of effective test kits. Furthermore, these findings can provide guidance for expanding the use of test kits, particularly with the growing availability of NSP-ELISA kits in the market.


Asunto(s)
Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Proteínas no Estructurales Virales , Animales , Ensayo de Inmunoadsorción Enzimática/métodos , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/aislamiento & purificación , Tailandia/epidemiología , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/epidemiología , Fiebre Aftosa/virología , Fiebre Aftosa/sangre , Bovinos , Proteínas no Estructurales Virales/inmunología , Anticuerpos Antivirales/sangre , Porcinos , Búfalos , Sensibilidad y Especificidad , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/sangre , Juego de Reactivos para Diagnóstico
4.
J Gen Virol ; 105(10)2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39422666

RESUMEN

Foot-and-mouth disease vaccination using inactivated virus is suboptimal, as the icosahedral viral capsids often disassemble into antigenically distinct pentameric units during long-term storage, or exposure to elevated temperature or lowered pH, and thus raise a response that is no longer protective. Furthermore, as foot-and-mouth disease virus (FMDV)'s seven serotypes are antigenically diverse, cross-protection from a single serotype vaccine is limited, and most existing mouse and bovine antibodies and camelid single-domain heavy chain-only antibodies are serotype-specific. For quality control purposes, there is a real need for pan-serotype antibodies that clearly distinguish between pentamer (12S) and protective intact FMDV capsid. To date, few cross-serotype bovine-derived antibodies have been reported in the literature. We identify a bovine antibody with an ultralong CDR-H3, Ab117, whose structural analysis reveals that it binds to a deep, hydrophobic pocket on the interior surface of the capsid via the CDR-H3. Main-chain and hydrophobic interactions provide broad serotype specificity. ELISA analysis confirms that Ab117 is a novel pan-serotype and conformational epitope-specific 12S reagent, suitable for assessing capsid integrity.


Asunto(s)
Anticuerpos Antivirales , Proteínas de la Cápside , Cápside , Virus de la Fiebre Aftosa , Virus de la Fiebre Aftosa/inmunología , Animales , Bovinos , Anticuerpos Antivirales/inmunología , Cápside/inmunología , Proteínas de la Cápside/inmunología , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Serogrupo , Reacciones Cruzadas , Epítopos/inmunología
5.
Viruses ; 16(9)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39339914

RESUMEN

Foot-and-mouth disease (FMD) is one of the most infectious viral transboundary diseases of livestock, which causes devastating global economic losses. Different enzyme-linked immunosorbent assays (ELISAs) are used for sero-surveillance of the foot-and-mouth disease virus (FMDV). However, more sensitive, accurate, and convenient ELISAs are still required to detect antibodies against FMDV serotypes. The primary goal of this study was to establish serotype-specific monoclonal antibody (mAb)-based blocking ELISAs (mAb-bELISAs) that would provide better performance characteristics or be equivalent in performance characteristics compared with a conventional polyclonal antibody (pAb)-based competitive ELISA (pAb-cELISA). Four mAb-bELISAs were developed using FMDV serotype-specific mAbs for the detection of anti-FMDV/O/A/Asia1/SAT2 antibodies. Using a 50% cut-off, all four mAb-bELISAs exhibited species-independent 99.74%, 98.01%, 96.59%, and 98.55% diagnostic specificity (DSp) and 98.93%, 98.25%, 100%, and 87.50% diagnostic sensitivity (DSe) for FMDV serotypes O, A, Asia1, and SAT2, respectively. In addition, a 100% DSe of serotypes O- and SAT2-specific mAb-bELISAs was observed for porcine sera when the cut-off was 30%. All mAb-bELISAs developed in this study displayed high repeatability/reproducibility without cross-reactivity. Finally, the diagnostic performance of mAb-bELISAs was found to be better than or equivalent to compared with pAb-cELISAs, suggesting that mAb-bELISAs can be used to replace existing pAb-ELISAs for the detection of antibodies against these four FMDV serotypes.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Sensibilidad y Especificidad , Serogrupo , Ensayo de Inmunoadsorción Enzimática/métodos , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/clasificación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Porcinos , Bovinos , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/inmunología , Ratones , Reproducibilidad de los Resultados
6.
Arch Razi Inst ; 79(1): 201-210, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39192966

RESUMEN

The most preferred method for the detection of foot-and-mouth disease (FMD) viral antigen and identification of viral serotype is the enzyme-linked immunosorbent assay (ELISA). Diagnostic tests with high sensitivity are necessary both to distinguish infected vaccinated animals and execute disease control programs for the identification of the carrier animals. The current strategies for the detection of FMD virus are mainly based on the capture antibody (sandwich) ELISA test. The usage of laying pullets as an animal bioreactor for the production of specific egg yolk antibodies (IgY) has increased in recent years due to its high yield, affinity, low price, and quick production turnover. The present study aimed to produce a concentrated and purified IgY polyclonal antibody to design a capture antibody ELISA kit against the FMD virus (FMDV) serotype A. At first, laying hens were immunized with inactivated FMDV serotype virus, and then, on days 14, 21, and 28 following vaccination, the eggs and sera were collected. Afterward, the IgY polyclonal antibodies were extracted and purified from the chicken egg yolk using a polyethylene glycol 6000-ethanol precipitation procedure. Extracts were filtered, purified by ion exchange chromatography, and dialyzed. The purified IgY concentration, estimated by Bradford assay, confirmed its presence by SDS-PAGE and Western blot and also its specific immune reaction by Ouchterlony double immunodiffusion and Dot blot tests. Moreover, for achieving the optimum concentration of antigen/antibody (sera) in sandwich ELISA, a checkerboard titration test was set up based on indirect ELISA results. Eventually, 119 previously confirmed samples (including 80 positive and 39 negative) by both real-time polymerase chain reaction (quantitative PCR, qPCR) and a commercial ELISA kit were used for evaluation of the sensitivity and accuracy of our developed Capture antibody ELISA kit. In this manner, the sensitivity and specificity of our designed kit were 100% and 98%, respectively. Accordingly, the present developed capture ELISA kit based on IgY had high sensitivity and specificity for FMD virus detection and it could be used in the future for both commercial detecting and serotyping applications.


Asunto(s)
Anticuerpos Antivirales , Pollos , Ensayo de Inmunoadsorción Enzimática , Fiebre Aftosa , Inmunoglobulinas , Enfermedades de las Aves de Corral , Animales , Ensayo de Inmunoadsorción Enzimática/veterinaria , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunoglobulinas/inmunología , Inmunoglobulinas/análisis , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/prevención & control , Fiebre Aftosa/virología , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Enfermedades de las Aves de Corral/diagnóstico , Enfermedades de las Aves de Corral/virología , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/aislamiento & purificación , Sensibilidad y Especificidad , Yema de Huevo/inmunología
7.
Int J Biol Macromol ; 277(Pt 4): 134366, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39098702

RESUMEN

Intact capsids of foot-and-mouth disease virus (FMDV) play a vital role in eliciting a protective immune response. Any change in the physico-chemical environment of the capsids results in dissociation and poor immunogenicity. Structural bioinfomatics studies have been carried out to predict the amino acids at the interpentameric region that resulted in the identification of mutant virus-like particles(VLPs) of FMDV serotype Asia1/IND/63/1972. The insect cell expressed VLPs were evaluated for their stability by sandwich ELISA. Among 10 mutants, S93H showed maximum retention of antigenicity at different temperatures, indicating its higher thermal stability as revealed by the in-silico analysis and retained the antigenic sites of the virus demonstrated by Sandwich ELISA. The concordant results of the liquid phase blocking ELISA for estimation of antibody titre of known sera with stable mutant VLP as antigen in place of virus antigen demonstrate its diagnostic potential. The stable mutant VLP elicited a robust immune response with 85.6 % protection in guinea pigs against virus challenge. The stabilized VLP based antigen requires minimum biosafety and cold storage for production and transit besides, complying with differentiation of infected from vaccinated animals. It can effectively replace the conventional virus handling during antigen production for prophylactic and diagnostic use.


Asunto(s)
Virus de la Fiebre Aftosa , Fiebre Aftosa , Serogrupo , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/genética , Animales , Fiebre Aftosa/prevención & control , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/inmunología , Cobayas , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Antígenos Virales/genética , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/química , Vacunas Virales/inmunología , Vacunas Virales/genética , Mutación
8.
Biologicals ; 87: 101785, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39121525

RESUMEN

Diagnostic assays that are able to detect foot-and-mouth disease (FMD) virus infection in the vaccinated population are essential tools in the progressive control pathway for the FMD. However, testing of serum samples using a single diagnostic assay may not completely substantiate freedom from the virus infection. Therefore, viral non-structural proteins (NSPs)-based various serological assays have been developed for the detection of FMD infection. Nevertheless, the NSPs-based ELISAs have been developed in the indirect-ELISA format, thereby necessitating the use of species-specific conjugated secondary-antibodies for the detection of anti-NSP antibodies in various FMD-susceptible species. Therefore, this study presents a novel recombinant 2B-NSP-based indirect ELISA, employing HRP-conjugated protein-A/G detection system which can detect anti-NSPs antibodies from multiple FMD-susceptible species in a single ELISA platform. Recombinant 2B (r2B) protein was expressed as His-SUMO tagged protein in the E. Coli cells and purified using NI-NTA affinity column chromatography. Using the r2B protein and HRP-conjugated protein A/G, an indirect ELISA was developed and validated for the detection of anti-2B antibodies in serum samples collected from multiple FMD-susceptible animal species with known FMD status. Further, a resampling based statistical technique has been reported for determination of optimal cut-off value for the diagnostic assay. Through this technique, the optimal cut-off of 44 percentage of positivity value was determined for the assay. At this optimal cut-off value, the developed diagnostic assay provided diagnostic sensitivity, specificity, and accuracy, positive and negative predictive values (PPV and NPV) of 92.35 %, 98.41 %, 95.21 %, 98.58 %, and 91.67 %, respectively. The assay was validated further by analyzing random serum samples collected across multi-locations in India. The assay can be used as a single platform for testing serum samples from different species of FMDV-susceptible animals and will be useful for NSP-based serosurveillance of FMDV.


Asunto(s)
Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Proteínas no Estructurales Virales , Virus de la Fiebre Aftosa/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Animales , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/inmunología , Fiebre Aftosa/sangre , Fiebre Aftosa/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Proteínas no Estructurales Virales/inmunología , Bovinos , Proteínas Recombinantes/inmunología , Porcinos , Especificidad de la Especie
9.
Front Immunol ; 15: 1440667, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39176090

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/inmunología
10.
Vet Microbiol ; 296: 110192, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032444

RESUMEN

VP1, a major immunogenic protein of foot-and-mouth disease virus (FMDV), facilitates viral attachment and entry into host cells. VP1 possesses critical epitope sequences responsible for inducing neutralizing antibodies but its expression using Saccharomyces cerevisiae has been hampered despite evidence that the presence of VP1 does not negatively impact the yeast's biology. In this study, we fused proteins to enhance VP1 expression using S. cerevisiae. Among short P1 chimeras containing VP1 including VP3-VP1 and VP2-VP1, VP3-VP1 fusion proteins showed higher expression levels than VP2-VP1. We subsequently designed new fusion proteins, of which 20 amino acids of N-terminal VP3 fused with VP1-Co1 (referred to 20aaVP3-VP1-Co1) showed the highest expression level. Lowering the culture temperature from 30 °C to 20 °C further enhanced fusion protein production. The highest expression level of 20aaVP3-VP1-Co1 was estimated to be 7.7 mg/L, which is comparable to other heterologous proteins produced using our S. cerevisiae expression system. Oral administration of the cell expressing 20aaVP3-VP1-Co1 induced VP1-specific IgG and IgA responses in mice. The S. cerevisiae-expressed 20aaVP3-VP1-Co1 fusion protein induced a significant immune response to the FMDV structural epitope protein, which opens the possibility of an oral FMDV vaccine.


Asunto(s)
Anticuerpos Antivirales , Proteínas de la Cápside , Virus de la Fiebre Aftosa , Fiebre Aftosa , Proteínas Recombinantes de Fusión , Saccharomyces cerevisiae , Vacunas Virales , Animales , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/genética , Ratones , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/genética , Anticuerpos Antivirales/sangre , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Administración Oral , Inmunización , Femenino , Codón , Anticuerpos Neutralizantes/inmunología , Ratones Endogámicos BALB C , Inmunoglobulina A
11.
J Vet Med Sci ; 86(9): 999-1007, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39069487

RESUMEN

The inactivated vaccine is effective in controlling foot-and-mouth disease (FMD), but it has drawbacks such as the need for a biosafety level 3 laboratory facility to handle live foot-and-mouth disease virus (FMDV), high production costs, and biological safety risks. In response to these challenges, we developed a new recombinant protein vaccine (2BT-pIgG-Fc) containing porcine IgG-Fc to enhance protein stability in the body. This vaccine incorporates two-repeat B-cell and one-single T-cell epitope derived from O/Jincheon/SKR/2014. Our study confirmed that 2BT-pIgG-Fc and a commercial FMDV vaccine induced FMDV-specific antibodies in guinea pigs at 28 days post-vaccination. The percentage inhibition (PI) value of 2BT-pIgG-Fc was 90.43%, and the commercial FMDV vaccine was 81.75%. The PI value of 2BT-pIgG-Fc was 8.68% higher than that of commercial FMDV vaccine. In pigs, the primary target animals for FMDV, all five individuals produced FMDV-specific antibodies 42 days after vaccination with 2BT-pIgG-Fc. Furthermore, serum from 2BT-pIgG-Fc-vaccinated pigs exhibited neutralizing ability against FMDV infection. Intriguingly, the 2BT-pIgG-Fc recombinant demonstrated FMDV-specific antibody production rates and neutralization efficiency similar to commercial inactivated vaccines. This study illustrates the potential to enhance vaccine efficacy by strategically combining well-known antigenic domains in the development of recombinant protein-based vaccines.


Asunto(s)
Anticuerpos Antivirales , Virus de la Fiebre Aftosa , Fiebre Aftosa , Inmunoglobulina G , Vacunas Sintéticas , Vacunas Virales , Animales , Virus de la Fiebre Aftosa/inmunología , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Vacunas Virales/inmunología , Porcinos , Cobayas , Vacunas Sintéticas/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Eficacia de las Vacunas , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virología , Epítopos de Linfocito T/inmunología , Proteínas Recombinantes/inmunología , Epítopos de Linfocito B/inmunología , Femenino , Fragmentos Fc de Inmunoglobulinas/inmunología
12.
Vet Res Commun ; 48(5): 3375-3380, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39031217

RESUMEN

Foot-and-mouth disease (FMD) is one of the most important animal diseases of economic significance globally. It is a highly infectious and contagious disease of cloven-hoofed animals including sheep and goat. For sero-diagnosis of FMD, recombinant antigen-based assays are considered as alternatives to conventional approaches such as the liquid phase blocking ELISA (LPBE). The early interventions towards control measures cannot be implemented unless the disease gets promptly diagnosed. It is relatively difficult to clinically diagnose FMD in goat due to the usual milder form or unapparent nature of symptoms. Under such situations where clinical samples are not available, demonstration of infection-specific FMD virus (FMDV) antibodies in serum sample may help identifying the animals exposed to the virus in retrospect. Antibody to 3AB nonstructural protein (NSP) has been considered to be the most reliable indicator for FMD diagnosis. The current study extended the earlier designed recombinant 3AB3 protein-based indirect ELISA originally validated on bovine serum samples to testing serum samples of goat. The performance of the indirect ELISA was validated using internationally accepted PrioCHECK® FMDV NS kit. The overall diagnostic sensitivity (DSn) of the indirect ELISA was estimated to be 95.52% (619/648), while the diagnostic specificity (DSp) on naïve and vaccinated animals varied at 98.06% (557/568) and 94.15% (435/462), respectively. In India, where FMD is prevalent and the goat population is so high, this 'in-house' optimized assay can be considered to be an adjunct in sero-epidemiological investigation of FMD in goat.


Asunto(s)
Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Aftosa , Fiebre Aftosa , Enfermedades de las Cabras , Cabras , Proteínas Recombinantes , Proteínas no Estructurales Virales , Animales , Ensayo de Inmunoadsorción Enzimática/veterinaria , Ensayo de Inmunoadsorción Enzimática/métodos , Fiebre Aftosa/diagnóstico , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Fiebre Aftosa/sangre , Enfermedades de las Cabras/diagnóstico , Enfermedades de las Cabras/virología , Enfermedades de las Cabras/inmunología , Virus de la Fiebre Aftosa/inmunología , Anticuerpos Antivirales/sangre , Proteínas no Estructurales Virales/inmunología , Proteínas Recombinantes/inmunología , Sensibilidad y Especificidad
13.
Am Nat ; 204(2): 133-146, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39008835

RESUMEN

AbstractInfectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask the following questions: How do viral and immune dynamics vary among strains? Which viral and immune parameters determine viral fitness within hosts? And how do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus's relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.


Asunto(s)
Búfalos , Virus de la Fiebre Aftosa , Fiebre Aftosa , Animales , Búfalos/virología , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/crecimiento & desarrollo , Fiebre Aftosa/transmisión , Fiebre Aftosa/virología , Fiebre Aftosa/inmunología , Interacciones Huésped-Patógeno/inmunología , Replicación Viral , Modelos Biológicos
14.
Prev Vet Med ; 230: 106282, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39033658

RESUMEN

Foot-and-mouth disease (FMD) is an important endemic disease in livestock in Southeast Asia. Transboundary movement of animals may result in the transnational disease spread. A major cattle market is located at the Thailand-Myanmar border, where most cattle imported from Myanmar are traded. In this study, we built a stochastic susceptible-exposed-infectious-recovered (SEIR) model to investigate the effectiveness of a private animal quarantine service center in preventing FMDV from entering the major cattle market. We computed with different parameters and found that, with 50 % vaccine effectiveness, the risk of releasing infected cattle to the market per batch was generally low during the quarantine period of 21 and 28 days, with the risk ranging from 0.071 to 0.078 and 0.032 to 0.036, respectively. Despite the best scenario, the zero-risk state is difficult to attain. The sensitivity analysis highlights that the percentage of immune animals before entering the quarantine centers and the vaccine effectiveness are important factors. In conclusion, the 21-day quarantine period mitigates the risk of FMDV introduction into the cattle market. This control measure should be rigorously maintained to sustainably prevent FMDV outbreaks through transboundary animal movements, especially among countries in FMD-endemic regions.


Asunto(s)
Enfermedades de los Bovinos , Fiebre Aftosa , Cuarentena , Procesos Estocásticos , Animales , Bovinos , Fiebre Aftosa/prevención & control , Fiebre Aftosa/epidemiología , Tailandia/epidemiología , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Cuarentena/veterinaria , Mianmar/epidemiología , Virus de la Fiebre Aftosa/inmunología , Comercio
15.
BMC Vet Res ; 20(1): 301, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971791

RESUMEN

BACKGROUND: Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140-158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines. RESULTS: This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. CONCLUSIONS: The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines.


Asunto(s)
Epítopos , Ferritinas , Virus de la Fiebre Aftosa , Fiebre Aftosa , Nanopartículas , Vacunas Virales , Animales , Cobayas , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/inmunología , Ferritinas/inmunología , Vacunas Virales/inmunología , Epítopos/inmunología , Ratones , Femenino , Ratones Endogámicos BALB C , Proteínas Recombinantes/inmunología , Proteínas de la Cápside
16.
Vaccine ; 42(25): 126066, 2024 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38876835

RESUMEN

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/métodos
17.
Aust Vet J ; 102(8): 407-415, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38840308

RESUMEN

With recent outbreaks of foot-and-mouth disease (FMD) in Indonesia and Bali, industry, government and public concern for its incursion into Australia is increasing. The potential impact of an outbreak on the agricultural industry and national economy could be devastating. To date, research conducted in relation to FMD in Australia predominantly concerns simulations and models performed to predict various outcomes. This project critically appraises the current literature regarding the simulated use of vaccination and its effectiveness for controlling the spread of FMD in Australia in the event of an outbreak. Findings from 10 modelling studies suggest that vaccination is effective at controlling the size and duration of an outbreak (under certain conditions), however, there is less clarity about cost-effectiveness.


Asunto(s)
Brotes de Enfermedades , Fiebre Aftosa , Ganado , Vacunación , Fiebre Aftosa/prevención & control , Fiebre Aftosa/epidemiología , Animales , Australia/epidemiología , Brotes de Enfermedades/veterinaria , Brotes de Enfermedades/prevención & control , Vacunación/veterinaria , Virus de la Fiebre Aftosa/inmunología , Análisis Costo-Beneficio , Vacunas Virales
18.
Artículo en Inglés | MEDLINE | ID: mdl-38910298

RESUMEN

Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.


Asunto(s)
Virus de la Fiebre Aftosa , Fiebre Aftosa , Evasión Inmune , Inmunidad Innata , Vacunas Virales , Animales , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/patogenicidad , Vacunas Virales/inmunología , Inmunidad Adaptativa , Humanos , Interacciones Huésped-Patógeno/inmunología , Variación Antigénica
19.
Vaccine ; 42(18): 3789-3801, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38714448

RESUMEN

Inactivated vaccines lack the capability to serologically differentiate between infected and vaccinated animals, thereby impeding the effective eradication of pathogen. Conversely, vaccines based on virus-like particles (VLPs) emulate natural viruses in both size and antigenic structure, presenting a promising alternative to overcome these limitations. As the complexity of swine infectious diseases increases, the increase of vaccine types and doses may intensify the stress response. This exacerbation can lead to diminished productivity, failure of immunization, and elevated costs. Given the critical dynamics of co-infection and the clinically indistinguishable symptoms associated with foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), there is a dire need for an efficacious intervention. To address these challenges, we developed a combined vaccine composed of three distinct VLPs, specifically designed to target SVA and FMDV serotypes O and A. Our research demonstrates that this trivalent VLP vaccine induces antigen-specific and robust serum antibody responses, comparable to those produced by the respective monovalent vaccines. Moreover, the immune sera from the combined VLP vaccine strongly neutralized FMDV type A and O, and SVA, with neutralization titers comparable to those of the individual vaccines, indicating a high level of immunogenic compatibility among the three VLP components. Importantly, the combined VLPs vaccines-immunized sera conferred efficient protection against single or mixed infections with FMDV type A and O, and SVA viruses in pigs. In contrast, individual vaccines could only protect pigs against homologous virus infections and not against heterologous challenges. This study presents a novel combined vaccines candidate against FMD and SVA, and provides new insights for the development of combination vaccines for other viral swine diseases.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Virus de la Fiebre Aftosa , Fiebre Aftosa , Picornaviridae , Enfermedades de los Porcinos , Vacunas de Partículas Similares a Virus , Vacunas Virales , Animales , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/inmunología , Porcinos , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Ratones , Picornaviridae/inmunología , Infecciones por Picornaviridae/prevención & control , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/veterinaria , Femenino , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Coinfección/prevención & control , Coinfección/inmunología
20.
Virology ; 596: 110103, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38781710

RESUMEN

In order to develop a safe and effective broad-spectrum vaccine for foot-and-mouth disease (FMDV), here, we developed a recombinant FMD multiple-epitope trivalent vaccine based on three distinct topotypes of FMDV. Potency of the vaccine was evaluated by immune efficacy in pigs. The results showed that the vaccine with no less than 25 µg of antigen elicited FMDV serotype O specific antibodies and neutralization antibodies by primary-booster regime, and offered immune protection to pigs. More importantly, the vaccine elicited not only the same level of neutralization antibodies against the three distinct topotypes of FMDV, but also provided complete protection in pigs from the three corresponding virus challenge. None of the fully protected pigs were able to generate anti-3ABC antibodies throughout the experiment, which implied the vaccine can offer sterilizing immunity. The vaccine elicited lasting-long high-level antibodies and effectively protected pigs from virulent challenge within six months of immunization. Therefore, we consider that this vaccine may be used in the future for the prevention and control of FMD.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Epítopos , Virus de la Fiebre Aftosa , Fiebre Aftosa , Serogrupo , Enfermedades de los Porcinos , Vacunas Sintéticas , Vacunas Virales , Animales , Virus de la Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa/genética , Fiebre Aftosa/prevención & control , Fiebre Aftosa/inmunología , Fiebre Aftosa/virología , Porcinos , Vacunas Virales/inmunología , Vacunas Virales/genética , Vacunas Virales/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/inmunología , Epítopos/inmunología , Epítopos/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Eficacia de las Vacunas
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