Vaccination Of Cattle Research Articles

Bovine Tuberculosis in Cattle: Vaccines, DIVA Tests, and Host Biomarker Discovery.

Bovine tuberculosis remains a major economic and animal welfare concern worldwide. Cattle vaccination is being considered as part of control strategies. This approach, used alongside conventional control policies, also requires the development of vaccine-compatible diagnostic assays to distinguish vaccinated from infected animals (DIVA). We discuss progress made on optimizing the only potentially available vaccine, bacille Calmette Guérin (BCG), and on strategies to improve BCG efficacy. We also describe recent advances in DIVA development based on the detection of host cellular immune responses by blood-testing or skin-testing approaches. Finally, to accelerate vaccine development, definition of host biomarkers that provide meaningful stage-gating criteria to select vaccine candidates for further testing is highly desirable. Some progress has also been made in this area of research, and we summarize studies that defined either markers predicting vaccine success or markers that correlate with disease stage or severity.

Safety and efficacy of reduced dose Brucella abortus strain- 19 vaccine in non-pregnant zebu cattle (Bos indicus) heifers

In India, brucellosis a re-emerging disease, is of public health and economic concern to dairy industry. Brucella abortus strain-19 vaccine is recommended as most effective vaccine for cattle and buffaloes, however application of full dose is restricted in adults due to persistence of antibody response that interfere with serological diagnosis. In the present study 120 seronegative female cattle (60 calves and 60 young heifers each in a group) were subjected for vaccination. In each age group, 40 animals were vaccinated subcutaneously with a reduced dose of B. abortus S-19 vaccine, 10 animals with standard dose and 10 animals served as controls. Animals were observed for local or systemic reactions after vaccination as well as during study period. Blood samples were collected on day 0, 21, 60, 90 post-vaccination for antibody response and cell mediated immunity (CMI). The study revealed that the reduced dose vaccine is safe with satisfactory humoral and CMI response comparable to that of the standard dose, in both the age groups of animals when administered subcutaneously. It was concluded that the B. abortus S-19 reduced dose vaccine is safe and effective in the young and non-pregnant cattle up to the age of 30 months.

Development of immune-diagnostic reagents to diagnose bovine tuberculosis in cattle

Bovine tuberculosis remains a major economic and animal welfare concern worldwide. As part of control strategies, cattle vaccination is being considered. This approach, used alongside conventional control policies, also requires the development of vaccine compatible diagnostic assays to distinguish infected from vaccinated animals (DIVA). In this review we discuss recent advances in DIVA development based on the detection of host cellular immune responses by blood testing or skin testing approaches.

Mass vaccination, immunity and coverage: modelling population protection against foot-and-mouth disease in Turkish cattle.

Foot-and-mouth disease (FMD) in Turkey is controlled using biannual mass vaccination of cattle. However, vaccine protection is undermined by population turnover and declining immunity. A dynamic model of the Turkish cattle population was created. Assuming biannual mass vaccination with a single-dose primary course, vaccine history was calculated for the simulated population (number of doses and time since last vaccination). This was used to estimate population immunity. Six months after the last round of vaccination almost half the cattle aged <24 months remain unvaccinated. Only 50% of all cattle would have received >1 vaccine dose in their life with the last dose given ≤6 months ago. Five months after the last round of vaccination two-thirds of cattle would have low antibody titres (<70% protection threshold). Giving a two-dose primary vaccination course reduces the proportion of 6–12 month old cattle with low titres by 20–30%. Biannual mass vaccination of cattle leaves significant immunity gaps and over-reliance on vaccine protection should be avoided. Using more effective vaccines and vaccination strategies will increase population immunity, however, the extent to which FMD can be controlled by vaccination alone without effective biosecurity remains uncertain.

Vaccination control programs for multiple livestock host species: an age-stratified, seasonal transmission model for brucellosis control in endemic settings.

BackgroundBrucella melitensis causes production losses in ruminants and febrile disease in humans in Africa, Central Asia, the Middle East and elsewhere. Although traditionally understood to affect primarily sheep and goats, it is also the predominant Brucella species that affects cows in some endemic areas. Despite this, no licensed vaccine is available specifically for use against B. melitensis in cows. The mainstay of most control programs is vaccination of sheep and goats with a live vaccine, Rev-1. The aim of this study was to investigate how critical vaccination of cows might be, in order to control B. melitensis on a mixed sheep-and-cattle farm.MethodsA dynamic, differential-equation, age-structured, seasonal model with births and deaths, was used to investigate whether vaccination of both sheep and cattle had an impact on time to elimination of brucellosis on an individual mixed species farm, when compared to vaccination of sheep only. The model was a Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model with an additional compartment for Persistently Infected (PI) individuals. Transmission parameters were fit based on a nation-wide probabilistic seroprevalence survey in Jordan.ResultsThe model predicted that it would take 3.5 years to eliminate brucellosis (to less than 0.5 % of adult sheep seropositive as a result of infection) on a mixed-species B. melitensis-endemic farm with the median field-study seroprevalence, following vaccination of both sheep and cattle, assuming a vaccine effectiveness of 80 %. Limiting the vaccination to sheep only, increased the time to 16.8 years. Sensitivity analysis showed that the finding that vaccination of cattle was of significant importance, was robust. Vaccine effectiveness had a strong influence on time to elimination.ConclusionsIn the absence of further data, vaccination of cattle should be considered essential in Brucella-endemic settings where mixed small ruminant and cattle flocks predominate. Further evidence that Brucella melitensis predominates in cattle in Jordan, as opposed to Brucella abortus, is needed in order to validate this model. The results may be applicable to other mixed-species settings with similar livestock management practices. These methods may be applied to other pathogens affecting multiple livestock species or with seasonal transmission.

Development of a Sterne-Based Complement Fixation Test to Monitor the Humoral Response Induced by Anthrax Vaccines.

Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals, and humans depend on the prevention in livestock, principally cattle, sheep, and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2–) B. anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF). The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test (CFT) to detect specific antibodies induced in animals vaccinated with Sterne 34F2. We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to correctly identify vaccinated animals. It proved to be a very sensitive and specific test. Moreover, the Sterne-based CFT offers many benefits with regard to costs, standardization and reproducibility of the assay procedure.

Transmission of foot and mouth disease at the wildlife/livestock interface of the Kruger National Park, South Africa: Can the risk be mitigated?

In Southern Africa, the African buffalo (Syncerus caffer) is the natural reservoir of foot and mouth disease (FMD). Contacts between this species and cattle are responsible for most of the FMD outbreaks in cattle at the edge of protected areas, which generate huge economic losses. During the late 1980’s and 90’s, the erection of veterinary cordon fences and the regular vaccination of cattle exposed to buffalo contact at the interface of the Kruger National Park (KNP), proved to be efficient to control and prevent FMD outbreaks in South Africa. However, since 2000, the efficiency of those measures has deteriorated, resulting in an increased rate of FMD outbreaks in cattle outside KNP, currently occurring more than once a year.Based on retrospective ecological and epidemiological data, we developed a stochastic quantitative model to assess the annual risk of FMD virus (FMDV) transmission from buffalo to cattle herds present at the KNP interface. The model suggests that good immunization of approximately 75% of the cattle population combined with a reduction of buffalo/cattle contacts is an efficient combination to reduce FMDV transmission to one infective event every 5.5 years, emulating the epidemiological situation observed at the end of the 20th century, before current failure of control measures. The model also indicates that an increasing number of buffalo present in the KNP and crossing its boundaries, combined with a reduction in the vaccination coverage of cattle herds at the interface, increases 3-fold the risk of transmission (one infective event per year).The model proposed makes biological sense and provides a good representation of current knowledge of FMD ecology and epidemiology in Southern Africa which can be used to discuss with stakeholders on different management options to control FMD at the wildlife livestock interface and updated if new information becomes available. It also suggests that the control of FMD at the KNP interface is becoming increasingly challenging and will probably require alternative approaches to control this disease and its economic impact.

QS-21 enhances the early antibody response to oil adjuvant foot-and-mouth disease vaccine in cattle.

PurposeOne of the most important tools against foot-and-mouth disease, a highly contagious and variable viral disease of cloven-hoofed animals, is vaccination. However, the effectiveness of foot-and-mouth disease vaccines on slowing the spread of the disease is questionable. In contrast, high potency vaccines providing early protection may solve issues with the spread of the disease, escaping mutants, and persistency. To increase the potency of the vaccine, additives such as saponin and aluminium hydroxide are used. However, the use of saponin with an oil adjuvant is not common and is sometimes linked to toxicity. QS-21, which is less toxic than Quil A, has been presented as an alternative for use with saponin. In this study, the addition of QS-21 to a commercially available foot-and-mouth disease water-in-oil-in-water emulsion vaccine was evaluated in cattle.Materials and MethodsAfter vaccination, serum samples were collected periodically over 3 months. Sera of the QS-21 and normal oil vaccine groups were compared via serum virus neutralization antibody titre and liquid phase blocking enzyme-linked immunosorbent assay antibody titre.ResultsThe results showed that there was a significant early antibody increase in the QS-21 group.ConclusionStrong early virus neutralizing antibody response will be useful for emergency or ring vaccinations against foot-and-mouth disease in target animals.

Efficacy of Expired Foot-and-mouth Disease O Type Vaccines in Cattle and Buffalo in Lao People’s Democratic Republic

Lao People's Democratic Republic (Lao PDR) submitted a request to Japan for 200,000 doses of expired foot-and-mouth disease (FMD) O type vaccines that were in storage for emergency use. Approximately 100,000 animals, consisting of both cattle and Asian water buffalo (Bubalus bubalus bubalis), received the same vaccine twice within one month in Xieng Khouang province in the northeast area of Lao PDR. Concurrently, the efficacy of three-month expired FMD O type vaccine (6PD50 O Manisa) was assessed in serum samples of 90 cattle and 31 buffalo from the field using a Liquid Phase Blocking-ELISA (LPBE) assay. Of these samples, 75 cattle (83.3%) and 24 buffalo (77.4%) were seropositive against the FMD virus (FMDV) O type before vaccination. Testing for non-structural protein (NSP) using the PrioCHECK FMD NS kit showed that many of the animals with high titers in the screening test before vaccination were FMDV-infected animals. Fifteen cattle and seven buffalo with titers 1:32 or under before vaccination exhibited high titers of antibody (1:45-1:1448) one month after the first vaccination and further increased titers (1:362-1:5792) one month after the second vaccination. Nearly all of the cattle (97.6%) had high titers to control FMD 14 months after the second vaccination. To date, no outbreak of FMD has been reported at the study site. Three-month expired FMD O type vaccines induced appropriate immune responses against FMD in both cattle and buffalo.

Development of inactivated Akabane and bovine ephemeral fever vaccine for cattle

Development of inactivated Akabane and bovine ephemeral fever vaccine for cattle

A Comparative Study on the Hemato-Biochemical and Immunological Effects of the Hexavalent FMD Vaccine Alone or in Combination with Trivalent FMD Vaccine in Cattle

Foot and mouth disease is the most contagious disease of mammals and has a great potential for causing severe economic loss in susceptible cloven-hoofed animals. Routine prophylactic vaccination in Egypt from 2012 till now has been conducted with Trivalent and/or hexavalent vaccine of MERIAL, against virus strains (O manisa + O-3039 + A Iran 05 + A Saudi 95 + Asia 1 + Sat2). This study aimed to evaluate the hemato-biochemical and immunological changes associated with the use of hexavalent vaccine alone or in combination with trivalent FMD vaccine. This study was carried out on 24 cattle divided into three groups eight cattle each. Group I served as control. Group II were selected from farms vaccinated with hexavalent FMD vaccine. Group III were selected from farms vaccinated with a combination of trivalent and hexavalent FMD vaccine. The results showed that both vaccinated groups showed a significant increase in total leukocytic count. Sera from hexavalent-trivalent vaccinated cattle demonstrated a significant increase in serum cortisol concentrations. Significant increase in serum activity of aspartate aminotransferase was recorded in animals vaccinated with a combination of hexavalent and trivalent vaccine. In addition, both regimes resulted in a significant increase in serum blood urea nitrogen compared to control. Both regimes induced a significant increase in serum levels of ceruloplasmin while phagocytic activity of neutrophils and phagocytic index was enhanced only by the hexavalent vaccine. Both vaccinated groups had significantly increased serum values of gamma globulins. These results suggested that hexavalent vaccine produced higher levels of safety and protective effects against FMD in cattle as compared to those produced by a combination of hexavalent and trivalent vaccines. It is also advisable to include the hexavalent vaccine within the program of obligatory and imperative vaccination against FMD.

Prime-booster vaccination of cattle with an influenza viral vector Brucella abortus vaccine induces a long-term protective immune response against Brucella abortus infection

This study analyzed the duration of the antigen-specific humoral and T-cell immune responses and protectiveness of a recently-developed influenza viral vector Brucella abortus (Flu-BA) vaccine expressing Brucella proteins Omp16 and L7/L12 and containing the adjuvant Montadine Gel01 in cattle. At 1 month post-booster vaccination (BV), both humoral (up to 3 months post-BV; GMT IgG ELISA titer 214±55 to 857±136, with a prevalence of IgG2a over IgG1 isotype antibodies) and T-cell immune responses were observed in vaccinated heifers (n=35) compared to control animals (n=35, injected with adjuvant/PBS only). A pronounced T-cell immune response was induced and maintained for 12 months post-BV, as indicated by the lymphocyte stimulation index (2.7±0.4 to 10.1±0.9cpm) and production of IFN-γ (13.7±1.7 to 40.0±3.0ng/ml) at 3, 6, 9, and 12 months post-BV. Prime-boost vaccination provided significant protection against B. abortus infection at 3, 6, 9 and 12 months (study duration) post-BV (7 heifers per time point; alpha=0.03–0.01 vs. control group). Between 57.1 and 71.4% of vaccinated animals showed no signs of B. abortus infection (or Brucella isolation) at 3, 6, 9 and 12 months post-BV; the severity of infection, as indicated by the index of infection (P=0.0003 to <0.0001) and rates of Brucella colonization (P=0.03 to <0.0001), was significantly lower for vaccinated diseased animals than appropriate control animals. Good protection from B. abortus infection was also observed among pregnant vaccinated heifers (alpha=0.03), as well as their fetuses and calves (alpha=0.01), for 12 months post-BV. Additionally, 71.4% of vaccinated heifers calved successfully whereas all pregnant control animals aborted (alpha=0.01). Prime-boost vaccination of cattle with Flu-BA induces an antigen-specific humoral and pronounced T cell immune response and most importantly provides good protectiveness, even in pregnant heifers, for at least 12 months post-BV.

Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge

The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×108 to 2.1×1011 particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R2=0.97) and viremia (R2=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R2=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.

Vaccination of calves with yeast- and bacterial-expressed paramyosin from the bovine lungworm Dictyocaulus viviparus.

Previously, vaccination of cattle with Escherichia coli-expressed bovine lungworm paramyosin (EcPMY) adjuvanted with Quil A resulted in considerable reduction in worm burden and larvae shedding (Strube et al., 2015). To further evaluate the protective potential of PMY, cattle vaccination trials were performed using either E. coli- (EcPMY) or Pichia pastoris-expressed PMY (PpPMY) with different adjuvants (Matrix-Q(™) or Quil A). Combinations EcPMY+Matrix-Q(™) (trial 1), PpPMY+Matrix-Q(™) (trial 2) and PpPMY+Quil A (trial 3) were tested against challenge infections with 2000 Dictyocaulus viviparus larvae. Even though GM worm burden and larvae shedding was lower in almost all vaccinated groups, there were high variations between individuals hampering significant differences. However, in all vaccinated groups, lungworms were significantly shorter compared with those in controls. In vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant (r)PMY revealed no significant proliferation following vaccinations or challenge infection. All vaccinated cattle showed a significant rise in specific antibodies, particularly IgG and its subclass IgG1, and detected the native lungworm PMY in immunoblots starting 2 weeks after the first vaccination. The use of a different rPMY-adjuvant combination or combined vaccination with additional recombinant antigens might be a promising future approach towards a new vaccine against lungworms in cattle.

Antibodies Directed against Shiga-Toxin Producing Escherichia coli Serotype O103 Type III Secreted Proteins Block Adherence of Heterologous STEC Serotypes to HEp-2 Cells

Shiga toxin-producing Escherichia coli (STEC) serotype O103 is a zoonotic pathogen that is capable of causing hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. The main animal reservoir for STEC is ruminants and hence reducing the levels of this pathogen in cattle could ultimately lower the risk of STEC infection in humans. During the process of infection, STECO103 uses a Type III Secretion System (T3SS) to secrete effector proteins (T3SPs) that result in the formation of attaching and effacing (A/E) lesions. Vaccination of cattle with STEC serotype O157 T3SPs has previously been shown to be effective in reducing shedding of STECO157 in a serotype-specific manner. In this study, we tested the ability of rabbit polyclonal sera against individual STECO103 T3SPs to block adherence of the organism to HEp-2 cells. Our results demonstrate that pooled sera against EspA, EspB, EspF, NleA and Tir significantly lowered the adherence of STECO103 relative to pre-immune sera. Likewise, pooled anti-STECO103 sera were also able to block adherence by STECO157. Vaccination of mice with STECO103 recombinant proteins induced strong IgG antibody responses against EspA, EspB, NleA and Tir but not against EspF. However, the vaccine did not affect fecal shedding of STECO103 compared to the PBS vaccinated group over the duration of the experiment. Cross reactivity studies using sera against STECO103 recombinant proteins revealed a high degree of cross reactivity with STECO26 and STECO111 proteins implying that sera against STECO103 proteins could potentially provide neutralization of attachment to epithelial cells by heterologous STEC serotypes.

Comparative aspects of immunity and vaccination in human and bovine trichomoniasis: a review.

Trichomonas vaginalis and Tritrichomonas foetus are important extracellular protozoans that cause, respectively, human and bovine venereal diseases. Trichomonads are extracellular parasites that primarily inhabit the genital tracts of the mammalian hosts where they overcome the mucus barrier and parasitize mucosa by contact-dependent or contact-independent cytotoxicity. Transient immunity is usually achieved by the host after clinical infection. At present, vaccination in cattle reduces infection rates and reproductive wastage in affected herds. After vaccination, immunoglobulin G (IgG) levels increase in systemic circulation while immunoglobulin A (IgA) levels rise in the vagina. Only moderate protection is conferred by means of vaccination. Future vaccine development strategies are needed for cattle to enhance the antigenic component or use adjuvant that strongly activates the innate immune response to produce safe and potent vaccines. This paper reviews the current knowledge of the immunology of trichomoniasis infection and the challenges and potential of vaccines in the control of the infection in human and bovine trichomoniasis.

Effect of injectable trace minerals (zinc, manganese, selenium, and copper) on the humoral and cell-mediated immune responses to vaccine antigens following administration of a modified-live viral vaccine in dairy calves

The benefits of administering injectable trace minerals (ITM; Zn, Mn, Cu, and Se) on animal health and performance have been previously assessed in dairy and beef cattle. Previous studies demonstrated that ITM improved humoral immune response to bovine herpesvirus l(BHV-l) following administration of a modified live virus (MLV) vaccine in cattle. The objective of this study was to evaluate the effect of an ITM supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to individual vaccine antigens in dairy calves receiving a MLV vaccine containing bovine viral diarrhea virus (BVDV), BHV1, parainfluenza virus 3 (PI3V), and bovine respiratory syncytial virus (BRSV).

Cattle NK Cell Heterogeneity and the Influence of MHC Class I.

Primate and rodent NK cells form highly heterogeneous lymphocyte populations owing to the differential expression of germline-encoded receptors. Many of these receptors are polymorphic and recognize equally polymorphic determinants of MHC class I. This diversity can lead to individuals carrying NK cells with different specificities. Cattle have an unusually diverse repertoire of NK cell receptor genes predicted to encode receptors that recognize MHC class I. To begin to examine whether this genetic diversity leads to a diverse NK cell population, we isolated peripheral NK cells from cattle with different MHC homozygous genotypes. Cytokine stimulation differentially influenced the transcription of five receptors at the cell population level. Using dilution cultures, we found that a further seven receptors were differentially transcribed, including five predicted to recognize MHC class I. Moreover, there was a statistically significant reduction in killer cell lectin-like receptor mRNA expression between cultures with different CD2 phenotypes and from animals with different MHC class I haplotypes. This finding confirms that cattle NK cells are a heterogeneous population and reveals that the receptors creating this diversity are influenced by the MHC. The importance of this heterogeneity will become clear as we learn more about the role of NK cells in cattle disease resistance and vaccination.

A novel bovine leukemia virus peptide vaccine targeting susceptible cattle-Production by 3-D modelling and nanotechnology

Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2 (HTLV-1 and -2), causes enzootic bovine leukosis (EBL), a disease characterized by a much extended course that often involves persistent lymphocytosis and culminates in B-cell lymphoma the future. Our previously study demonstrated that cattle which had bovine major histocompatibility complex (BoLA)-DRB3*1601/*1601 genotype tend to onset EBL and indicates high proviral load. One of the major problems to develop the BLV vaccine is unstable effect of the vaccine because of the individual difference for disease susceptibility, we here tried to develop the BLV vaccine for disease susceptible cattle. Firstly, we determined the Th1 epitope of BLV antigens against disease susceptible cattle using a total 118 kind of peptides corresponding to GAG p15, p24 and p12, and ENV gp51 and gp30. Furthermore, we performed the optimization of our determined Th1 epitopes by antigen peptide modeling using in silico screening to resolve low affinity binding between peptide and susceptible BoLA DR molecule. Moreover, to resolve low stability of peptide and induce effectively Th1 immunity, we capsulated our optimized peptides, p12-4R1 and gp51R1, by Carbonate apatite (CO3Ap) because out of three kinds of nano-particles, such as CO3Ap, Cholesterol-modified gelatin and MGlu-HPG-Liposome, CO3Ap most strongly induced in all of Dendritic cell incorporation, antibody production and cellular immunity. Finally, we demonstrated the induction of antigen-specific cell-mediated immune response in mice by both of subcutaneous vaccination and intradermal vaccination of p12-4R1/gp51R1 peptide-conjugated CO3Ap. Collectively, we succeeded to produce a novel peptide vaccine targeting disease susceptible cattle which can induce antigen-specific cellmediated immune response in vivo.

Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments.