Foot-and-mouth Disease Virus Vaccine Research Articles

Effect of vaccination against foot-and-mouth disease during mid-pregnancy on the neutralizing antibody response in the cow.

As pregnancy can adversely affect the immune response of vaccination against foot and mouth disease virus (FMDV) due to physiological immunosuppressive milieu, we tested the effect of FMDV vaccination during mid-gestation on the antibody response. Pregnant and non-pregnant cows of crossbred and indigenous breed (n=28/group) were vaccinated with inactivated FMD vaccine covering O, A, and Asia1 serotypes and the sera were harvested at weekly interval till day 42 post-vaccination. Virus neutralization test (VNT) was done and the analysis of log10 VN50 antibody titer by mixed model ANOVA indicated that pregnancy did not significantly affect the log10 VN50 titer for FMDV serotype O and Asia1. Though pregnancy significantly decreased the titer for FMDV serotype A, the effect size was small. The experiment was repeated in purebred HF cows (n=10/group) and the results were reproducible. It was concluded that mid-pregnancy would not hamper the herd immunity to FMD vaccination in the cow.

Detection of anti-3AB3 non-structural protein antibodies in foot-and-mouth disease virus vaccinated buffaloes at a semi-organized farm of Madhya Pradesh in India

Foot-and-mouth disease (FMD), one of the most important viral diseases of cloven-hoofed animals in India, is caused by FMD virus (FMDV) which belongs to Aphthovirus in the family Picornaviridae. There are three serotypes of FMDV (O, A and Asia 1) circulating amongst the livestock population of India. FMD is characterized by the formation of vesicles especially over the tongue and in between the interdigital space. FMD-affected animals with tongue lesions are reluctant to feed and subsequently yield less milk as well as affected animals never regain their production status causing huge economic losses to the animal owners. In the present study, random whole blood samples from FMD-vaccinated 38 adult buffaloes were collected in sterile containers of a semi-organized buffalo farm of Madhya Pradesh in India. Purified FMD vaccines only elicit antibodies (that are protective) against structural proteins of FMDV while natural FMDV infection invokes antibodies against both structural and non-structural proteins. Serum samples were employed in recombinant 3AB3 non-structural protein-based enzyme-linked immunosorbent assay (3AB3 NSP-ELISA kit provided by ICAR-Directorate of FMD, Mukteshwar) for differentiation of FMD-infected and vaccinated animals (DIVA). A total of 10.53% (4/38) serum samples tested positive in DIVA. Largely the vaccinated animals remained protected as no clinical signs of the disease were observed reiterating the importance of regular FMDV vaccination in animals at semi-organized dairy farms.

Impact of Different Foot and Mouth Disease Vaccine Schemes in Cross-Neutralization Against Heterologous Serotype O Strains in Cattle.

The high antigenic variability of the foot-and-mouth disease virus (FMDV) represents a challenge for developing prophylactic strategies, stressing the need for research into vaccines offering broad protection against a range of virus strains. Here, the heterotypic cross-reaction using different vaccine schemes against serotype O strains was studied, evaluating the impact of revaccination, antigen dose, and incorporation of additional FMDV serotypes. Naïve cattle were immunized with seven distinct FMDV vaccines, receiving three doses of the same formulation at 0, 28, and 56 days post-primary vaccination (dpv). Serum samples were collected up to 70 dpv and tested by a virus-neutralizing test against serotype O strains from a South American lineage and two strains representative of two Asian lineages. Our results showed that vaccines containing the ME-SA topotype O1/Campos strain developed cross-neutralizing responses against the two Asian viruses after the first vaccination. In contrast, significant heterotypic neutralizing antibody titers against the homologous topotype strain were only found after the second vaccination, indicating that the phylogenic relationship may differ from the antigenic profiles for these two viruses. The amount of the O1/Campos strain and the revaccination were essential factors for neutralization against the homologous- and heterologous-type O FMDV viruses. The strain composition of the vaccine was only relevant for cross-neutralization against one of the Asian strains, suggesting potential intra-serotypic divergences for this pattern.

Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus.

It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotypes O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and/or Asia1 by dissecting 216 common clonotypes of two serotypes O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved "RGDL" motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine.

Establishment of the Foot-and-Mouth Disease Virus Type Asia1 Expressing the HiBiT Protein: A Useful Tool for a NanoBiT Split Luciferase Assay.

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein-protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies.

Foot and mouth disease vaccine efficacy in Africa: a systematic review and meta-analysis.

Several factors, such as diverse serotypes, vaccination methods, weak biosecurity, and animal movements, contribute to recurrent Foot-and-Mouth Disease Virus (FMDV) outbreaks in Africa, establishing endemicity. These outbreaks cost over $2 billion annually, prompting a high-priority focus on FMDV vaccination. Despite extensive efforts, vaccine efficacy varies. This study aims to evaluate routine foot and mouth disease (FMD) vaccines in Africa via systematic review and meta-analysis. A systematic review and meta-analysis were carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted to assess the efficacy of FMDV vaccination using the meta for package of R. Vaccinated animals have roughly a 69.3% lower chance of FMDV infection compared to unvaccinated animals, as indicated by the pooled results from the random-effects model, which showed a risk ratio (RR) of 0.3073. There was a statistically significant heterogeneity (p < 0.05) across all of the included articles. Overall findings suggest that if properly planned and implemented, FMDV vaccination programs and strategies in Africa could help control the spread of the disease throughout the continent and beyond.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus

The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Intradermal Inoculation of Inactivated Foot-and-Mouth Disease Vaccine Induced Effective Immune Responses Comparable to Conventional Intramuscular Injection in Pigs.

All pigs in the Republic of Korea are given the foot-and-mouth disease virus (FMDV) vaccine intramuscularly (IM) as part of the country's vaccination policy. However, the IM administration of the FMDV vaccine to pig results in residual vaccine components in the muscle and undesirable changes in muscle and soft tissues, causing economic losses in swine production. In this study, we evaluated whether intradermal (ID) vaccination could be proposed as an alternative to IM administration. ID vaccination (0.2 mL on each side of the neck muscle) and IM vaccination (2 mL on each side of the neck muscle) were performed twice, separated by 14 days, using a commercial FMD vaccine in specific-pathogen-free pigs. We observed growth performance, gross and microscopic lesions at the inoculation site, FMDV-specific antibodies, and neutralizing antibodies for 35 days after vaccination. Side effects on the skin grossly appeared following ID administration, but most were reduced within two weeks. All ID-vaccinated pigs showed inflammatory lesions limited to the dermis, but IM-vaccinated pigs had abnormal undesirable changes and pus in the muscle. ID-vaccinated pigs performed comparably to IM-vaccinated pigs in terms of growth, FMD virus-specific antibodies, protection capability against FMDV, and T-cell induction. This study demonstrated that the ID inoculation of the inactivated FMD vaccine induced immune responses comparable to an IM injection at 1/10 of the inoculation dose and that the inoculation lesion was limited to the dermis, effectively protecting against the formation of abnormal undesirable changes in muscle and soft tissues.

Enhanced antigen-specific CD8 T cells contribute to early protection against FMDV through swine DC vaccination.

Foot-and-mouth disease virus (FMDV) remains a challenge for cloven-hooved animals. The currently licensed FMDV vaccines induce neutralizing antibody (NAb)-mediated protection but show defects in the early protection. Dendritic cell (DC) vaccines have shown great potency in inducing rapid T-cell immunity in humans and mice. Whether DC vaccination could enhance early protection against FMDV has not been elaborately explored in domestic pigs. In this study, we employed DC vaccination as an experimental approach to study the roles of cellular immunity in the early protection against FMDV in pigs. Autologous DCs were differentiated from the periphery blood mononuclear cells of each pig, pulsed with inactivated FMDV (iFMDV-DC) and treated with LPS, and then injected into the original pigs. The cellular immune responses and protective efficacy elicited by the iFMDV-DC were examined by multicolor flow cytometry and tested by FMDV challenge. The results showed that autologous iFMDV-DC immunization induced predominantly FMDV-specific IFN-γ-producing CD4+ T cells and cytotoxic CD8+ T cells (CTLs), high NAb titers, compared to the inactivated FMDV vaccine, and accelerated the development of memory CD4 and CD8 T cells, which was concomitantly associated with early protection against FMDV virulent strain in pigs. Such early protection was associated with the rapid proliferation of secondary T-cell response after challenge and significantly contributed by secondary CD8 effector memory T cells. These results demonstrated that rapid induction of cellular immunity through DC immunization is important for improving early protection against FMDV. Enhancing cytotoxic CD8+ T cells may facilitate the development of more effective FMDV vaccines.IMPORTANCEAlthough the currently licensed FMDV vaccines provide NAb-mediated protection, they have defects in early immune protection, especially in pigs. In this study, we demonstrated that autologous swine DC immunization augmented the cellular immune response and induced an early protective response against FMDV in pigs. This approach induced predominantly FMDV-specific IFN-γ-producing CD4+ T cells and cytotoxic CD8+ T cells, high NAb titers, and rapid development of memory CD4 and CD8 T cells. Importantly, the early protection conferred by this DC immunization is more associated with secondary CD8+ T response rather than NAbs. Our findings highlighted the importance of enhancing cytotoxic CD8+ T cells in early protection to FMDV in addition to Th1 response and identifying a strategy or adjuvant comparable to the DC vaccine might be a future direction for improving the current FMDV vaccines.

Evaluation of vaccine efficacy with 2B/T epitope conjugated porcine IgG-Fc recombinants against foot-and-mouth disease virus

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.

Recombinant bacteriophage T4 displaying key epitopes of the foot-and-mouth disease virus as a novel nanoparticle vaccine

Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that has caused significant economic losses in the livestock industry. Peptide vaccines engineered with the protective epitopes of FMDV have provided a safer alternative for disease prevention than the traditional inactivated vaccines. However, the immunogenicity of the peptide is usually poor and therefore an adjuvant is required. Here, we showed that recombinant T4 phages displaying the B-cell epitope of the FMDV VP1 protein (VP1130-158), without additional adjuvants, induced similar levels of antigen-specific IgG1 but higher levels of IgG2a compared to the peptide vaccine. Incorporation of a CD4+ T cell epitope, either 3A21-35 of FMDV 3A protein or P2830-844 of tetanus toxoid, further enhanced the immunogenicity of VP1-T4 phage nanoparticles. Interestingly, the extrinsic adjuvant cannot enhance the immunogenicity of the nanoparticles, indicating the intrinsic adjuvant activities of T4 phage. Furthermore, the recombinant T4 phage can be produced on a large scale within a short period of time at a relatively low-cost using Escherichia coli, heralding its potential in the development of a safe and effective FMDV vaccine.

Increases in Cellular Immune Responses Due to Positive Effect of CVC1302-Induced Lysosomal Escape in Mice.

This study found a higher percentage of CD8+ T cells in piglets immunized with a CVC1302-adjuvanted inactivated foot-and-mouth disease virus (FMDV) vaccine. We wondered whether the CVC1302-adjuvanted inactivated FMDV vaccine promoted cellular immunity by promoting the antigen cross-presentation efficiency of ovalbumin (OVA) through dendritic cells (DCs), mainly via cytosolic pathways. This was demonstrated by the enhanced levels of lysosomal escape of OVA in the DCs loaded with OVA and CVC1302. The higher levels of ROS and significantly enhanced elevated lysosomal pH levels in the DCs facilitated the lysosomal escape of OVA. Significantly enhanced CTL activity levels was observed in the mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8+ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigens. These studies shed new light on the development of immunopotentiators to improve cellular immunity induced by vaccines.

The Application of the Gibson Assembly Method in the Production of Two pKLS3 Vector-Derived Infectious Clones of Foot-and-Mouth Disease Virus.

The construction of a full-length infectious clone, essential for molecular virological study and vaccine development, is quite a challenge for viruses with long genomes or possessing complex nucleotide sequence structures. Herein, we have constructed infectious clones of foot-and-mouth disease virus (FMDV) types O and A by joining each viral coding region with our pKLS3 vector in a single isothermal reaction using Gibson Assembly (GA). pKLS3 is a 4.3-kb FMDV minigenome. To achieve optimal conditions for the DNA joining, each FMDV coding sequence was divided into two overlapping fragments of approximately 3.8 and 3.2 kb, respectively. Both DNA fragments contain the introduced linker sequences for assembly with the linearized pKLS3 vector. FMDV infectious clones were produced upon directly transfecting the GA reaction into baby hamster kidney-21 (BHK-21) cells. After passing in BHK-21 cells, both rescued FMDVs (rO189 and rNP05) demonstrated growth kinetics and antigenicity similar to their parental viruses. Thus far, this is the first report on GA-derived, full-length infectious FMDV cDNA clones. This simple DNA assembly method and the FMDV minigenome would facilitate the construction of FMDV infectious clones and enable genetic manipulation for FMDV research and custom-made FMDV vaccine production.

Preliminary validation of a single-spot version of a solid-phase competition ELISA for the detection of southern African territories foot-and-mouth disease serotype exposure in goats

Preliminary validation of a single-spot version of a solid-phase competition ELISA for the detection of southern African territories foot-and-mouth disease serotype exposure in goats

An anti-picornaviral strategy based on the crystal structure of foot-and-mouth disease virus 2C protein.

The foot-and-mouth disease virus (FMDV) 2C protein shares conserved motifs with enterovirus 2Cs despite low sequence identity. Here, we determine the crystal structure of an FMDV 2C fragment to 1.83Å resolution, which comprises an ATPase domain, a region equivalent to the enterovirus 2C zinc-finger (ZFER), and a C-terminal domain harboring a loop (PBL) that occupies a hydrophobic cleft (Pocket) in an adjacent 2C molecule. Mutations at ZFER, PBL, and Pocket affect FMDV 2C ATPase activity and are lethal to FMDV infectious clones. Because the PBL-Pocket interaction between FMDV 2C molecules is essential for its functions, we design an anti-FMDV peptide derived from PBL (PBL-peptide). PBL-peptide inhibits FMDV 2C ATPase activity, binds FMDV 2C with nanomolar affinity, and disrupts FMDV 2C oligomerization. FMDV 2C targets lipid droplets (LDs) and induces LD clustering in cells, and PBL-peptide disrupts FMDV 2C-induced LD clustering. Finally, we demonstrate that PBL-peptide exhibits anti-FMDV activity in cells.

Biodegradable Imiquimod-Loaded Mesoporous Organosilica as a Nanocarrier and Adjuvant for Enhanced and Prolonged Immunity against Foot-and-Mouth Disease Virus in Mice.

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 μg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, SOMSN-IMQ@FMDV can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that SOMSN-IMQ@FMDV triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes in vivo. Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.

Proof of Proficiency of Decentralized Foot-and-Mouth Disease Virus Diagnostics in Germany.

A proficiency test was performed to verify that the regional veterinary laboratories in Germany can provide reliable foot-and-mouth disease virus (FMDV) diagnostics. Overall, 24 samples were to be analyzed for FMDV-specific nucleic acids by real-time RT-PCR, and 16 samples had to be tested by ELISA for antibodies against non-structural proteins of FMDV. For both methods, a range of dilutions of the original materials (inactivated FMDV vaccine or convalescent serum from infected animals, respectively) was prepared, and negative samples were included as well. All 23 participating laboratories were able to detect FMDV genome down to a dilution of 1:100,000 of the vaccine preparation. Even at a dilution of 1:1,000,000, FMDV genome was detected by more than half of the participants. With the antibody ELISA, all sera were correctly identified by all participating laboratories. No false-positive results were returned with either method. All participating laboratories were found to be fully proficient in FMDV diagnostics.

Exploring foot-and-mouth disease virus antibody interactions using biolayer interferometry

Foot-and-mouth disease virus (FMDV) vaccines protect animals from infection by inducing antibodies. The level of neutralising antibody induced in response to vaccination (or infection), as measured by a virus neutralisation test, is an important parameter with regards to the level of protection afforded against subsequent challenge. However, in addition to overall titre, antibody avidity also represents a crucial metric when assessing the protective efficacy of antibodies. In this project we investigated the use of biolayer interferometry (BLI) to measure the avidity of FMDV antibodies to FMDV antigens. Antibodies targeting site I of the FMDV particle were detected using a commercially synthesised biotinylated peptide. In contrast, the entire antigenic landscape of the FMDV particle was represented by biotinylated FMDV capsids. The antigens were loaded onto Octet streptavidin biosensors at an optimal concentration prior to dipping into antibodies. The sera from different animals varied in avidity, reflecting the quantitative differences in avidity that exist between individual animals in response to FMDV vaccines. Interestingly, the Kdis values obtained for site I vs the entire capsid were different, supporting the importance of other sites beyond site I. Similarly, monoclonal antibodies targeting distinct, known antigenic sites on the capsid surface also resulted in different avidities. The BLI methodology reported here offers a useful approach by which to investigate the strength of antibody interactions at specific sites. In conjunction with recombinant technology, BLI will help aid in investigations into the relative importance of the different antigenic sites with regards to inducing a protective response.

Effect of the Faradarmani Consciousness Field on immune response induced by an inactivated vaccine against Foot and Mouth disease virus (FMDV) in rats and replication of FMDV in vitro

Foot-and-mouth disease (FMD) is one of the highest risk factors affecting the animal industry throughout the world. Currently, available commercial FMD vaccines have numerous limitations, such as slow induction and short-term maintenance of antibody titers. Therefore, a novel approach is needed that can induce high neutralizing antibody titers to protect the host in the early stages of FMD virus (FMDV) infection and maintain high antibody titers for long periods after one vaccination dose. There are several T-Consciousness Fields (TCFs), introduced by Mohammad Ali Taheri. TCFs are not matter or energy, so they cannot be measured directly. However, we can evaluate their effects indirectly through several reproducible experiments in the laboratory. The present study aimed to evaluate the effect of Faradarmani CF as a type of the TCFs on FMDV replication, titer, and RNA copy number as well as the humoral immune response against two types of inactivated FMDV vaccines with different adjuvants in rats. Two types of FMD vaccines with different adjuvants (Freund and Alum) were prepared, and then 30 male Wistar rats were immunized with vaccines. Rats were divided into 6 groups (n=5 per group). Four groups of rats were studied using the different combinations of treatments and two groups served as positive and negative controls. Vaccination intervals were every 14 days three times. Serum neutralization test (SN) and Enzyme-linked immunosorbent assay (ELISA) were used to assess changes in antibody levels in the serum samples of rats after each immunization. The results showed that Faradarmani CF induced the replication of the virus in vitro. In addition, antibody levels in treated groups under both Freund adjuvant and Alum adjuvant vaccines increased significantly compared to groups without Faradarmani CF treatment. In conclusion, our data suggest that Faradarmani CF may provide an effective approach to increase the success of immunization and vaccination against FMDV serotype O. It is recommended that the effects of TCFs on different types of vaccines be investigated.

Avidity of Polyclonal Antibodies to Foot-and-Mouth Disease Virus in Bovine Serum Measured Using Bio-Layer Interferometry.

Foot-and-mouth disease (FMD) is a disease of cloven-hoofed livestock caused by FMD virus (FMDV). FMD can be controlled through the use of inactivated vaccines, and it is well established that the protection afforded by FMD vaccines correlates strongly with neutralising antibody titres. However, the overall strength of binding, referred to as avidity, is also an important parameter with respect to the ability of antibodies to neutralise virus infection, and there is evidence that avidity can affect the level of protection afforded by FMDV vaccines. Here, as an alternative to modified enzyme-linked immunosorbent assays (avidity ELISAs) incorporating a chaotropic wash step, we used bio-layer interferometry (BLI) to measure the avidity of bovine polyclonal antibodies against FMDV capsids. We conducted preliminary experiments using recombinant FMDV capsids, as well as peptides representing antigenic loops, to demonstrate that the binding of monoclonal antibodies targeting specific antigenic sites could be detected using BLI. Subsequent experiments using polyclonal sera derived from FMD vaccinated cattle provided evidence of a positive correlation between the neutralising titre of the serum and the avidity as measured by BLI. Furthermore, we observed an increase in BLI avidity, as well as in the titre, in vaccinated animals upon challenge with the live virus.