Bovis Vaccine Research Articles

A 2 × 2 factorial randomized controlled trial of a commercial M. bovis (CMB) vaccine and a conditionally licensed M. bovoculi vaccine (CLMB) to prevent IBK

Infectious bovine keratoconjunctivitis (IBK) is an economically important disease of beef cattle. Currently, there is little pub­lic evidence from randomized controlled trials that the differ­ent vaccines and vaccination regimes available to prevent IBK in cattle are effective, including autogenous and commercial vaccines directed at Moraxella bovis or Moraxella bovoculi. The combined use of a commercial M. bovis (CMB) vaccine and a conditionally licensed M. bovoculi vaccine (CLMB) has yet to be publicly evaluated.

An intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis

Mucosal vaccines have the potential to elicit protective immune responses at the point of entry of respiratory pathogens, thus preventing even the initial seed infection. Unlike licensed injectable vaccines, mucosal vaccines comprising protein subunits are only in development. One of the primary challenges associated with mucosal vaccines has been identifying and characterizing safe yet effective mucosal adjuvants that can effectively prime multi-factorial mucosal immunity. In this study, we tested NanoSTING, a liposomal formulation of the endogenous activator of the stimulator of interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as a mucosal adjuvant. We formulated a vaccine based on the H1 antigen (fusion protein of Ag85b and ESAT-6) adjuvanted with NanoSTING. Intranasal immunization of NanoSTING-H1 elicited a strong T-cell response in the lung of vaccinated animals characterized by (a) CXCR3+ KLRG1− lung resident T cells that are known to be essential for controlling bacterial infection, (b) IFNγ-secreting CD4+ T cells which is necessary for intracellular bactericidal activity, and (c) IL17-secreting CD4+ T cells that can confer protective immunity against multiple clinically relevant strains of Mtb. Upon challenge with aerosolized Mycobacterium tuberculosis Erdman strain, intranasal NanoSTING-H1 provides protection comparable to subcutaneous administration of the live attenuated Mycobacterium bovis vaccine strain Bacille–Calmette–Guérin (BCG). Our results indicate that NanoSTING adjuvanted protein vaccines can elicit a multi-factorial immune response that protects from infection by M. tuberculosis.

Diversity and antigenic potentials of Mycoplasmopsis bovis secreted and outer membrane proteins within a core genome of strains isolated from North American bison and cattle.

Mycoplasmopsis bovis is a worldwide economically important pathogen of cattle that can cause or indirectly contribute to bovine respiratory disease. M. bovis is also a primary etiological agent of respiratory disease in bison with high mortality rates. A major challenge in the development of an efficacious M. bovis vaccine is the design of antigens that contain both MHC-1 and MHC-2 T-cell epitopes, and that account for population level diversity within the species. Publicly available genomes and sequence read archive libraries of 381M. bovis strains isolated from cattle (n=202) and bison (n=179) in North America were used to identify a core genome of 575 genes, including 38 that encode either known or predicted secreted or outer membrane proteins. The antigenic potentials of the proteins were characterized by the presence and strength of their T-cell epitopes, and their protein variant diversity at the population-level. The proteins had surprisingly low diversity and varying predictive levels of T-cell antigenicity. These results provide a reference for the selection or design of antigens for vaccine testing against strains infecting North American cattle and bison.

Use of recombinant proteins for the diagnosis and prevention of Mycoplasma bovis: a systematic review.

Mycoplasma bovis is a highly contagious pathogen that causes various diseases in herd animals, negatively impacting reproduction, production, and milk yield. Effective diagnostic methods and vaccine development are critical for controlling M. bovis outbreaks. This systematic review aimed to evaluate diagnostic alternatives and vaccine compounds based on recombinant proteins. Following the PRISMA protocol, a systematic search was conducted in the SciELO, PubMed, and CAPES Periodicals Portal databases. Inclusion criteria included studies published between 2008 and 2023 that involved (1) the use of recombinant proteins for M. bovis identification or vaccine production, (2) biological samples, (3) availability in the selected databases, (4) in vitro or in vivo experimental designs, and (5) English-language publications. Ten of the initial 53 studies screened met the inclusion criteria. Of these, four studies focused on diagnostic approaches and six on vaccine development. Diagnostic studies predominantly used an indirect enzyme-linked immunosorbent assay (ELISA) with recombinant proteins, achieving over 90% sensitivity and specificity in detecting M. bovis infections. In contrast, the development of recombinant vaccines has shown limited success, with challenges in identifying effective adjuvants and optimizing conditions for protective immunity. While recombinant protein-based diagnostics have proven effective, developing a successful vaccine against M. bovis remains elusive. Further research is necessary to refine vaccine formulations, including selecting suitable adjuvants and challenge models to enhance protective efficacy against M. bovis infections.

Babesia bovis RON2 binds to bovine erythrocytes through a highly conserved epitope

B. bovis invasion of bovine erythrocytes requires tight junction formation involving AMA-1/RON2 complex interaction. RON2 has been considered a vaccine candidate since antibodies targeting the protein can inhibit parasite invasion of target cells; however, the mechanism controlling B. bovis RON2 interaction with red blood cells is not yet fully understood. This study was thus aimed at identifying B. bovis RON2 protein regions associated with interaction with bovine erythrocytes. Natural selection analysis of the ron2 gene identified predominantly negative selection signals in the C-terminal region. Interestingly, protein-cell and competition assays highlighted the RON2-C region’s role in peptide 42918-mediated erythrocyte binding, probably to a sialoglycoprotein receptor. This peptide (1218SFIMVKPPALHCVLKPVETL1237) lies within an intrinsically disordered region of the RON2 secondary structure flanked by two helical residues. The study provides, for the first time, valuable insights into RON2’s role in interaction with its target cells. Future studies are required for studying the peptide’s potential as an anti-B. bovis vaccine component.

Efficacy of heat-inactivated Mycobacterium bovis vaccine delivered to European badgers (Meles meles) through edible bait

Badgers (Meles meles) are a major tuberculosis (TB) reservoir in Europe, with the potential to transmit infection to cattle. Here we assessed whether a recently described oral tuberculosis vaccine based on heat-inactivated Mycobacterium bovis (HIMB), delivered as edible baits, can protect badgers from infection. Eight badgers were given individually five baits, each one consisting of a ball of peanut butter, natural peanut and oat flakes including a dose of the vaccine containing 5 × 107 colony-forming units. In parallel, a control group of seven badgers did not receive the vaccine. One month and a half later a second dose of the vaccine was offered to the vaccinated group. Ninety-four days after the second dose, all badgers were challenged with M. bovis (103 colony-forming units per animal) delivered endobronchially to the right middle lung lobe. Clinical, immunological, pathological and bacteriological variables were measured throughout the whole study to assess the efficacy of the vaccine. Two vaccinated animals showed high bacterial load of M. bovis and worsening of pathological lesions of TB. Conversely, the other six vaccinated animals showed slight improvement in bacterial load and pathology with respect to the control group. These results suggest that delivering the TB vaccine via food bait can partially protect wild badger populations, although vaccination can lead to either protection or tolerization, likely depending on the animal's immune status and general condition at the time of vaccination. Further optimization of the vaccination trial/strategy is needed to reduce the rate of tolerization, such as altering vaccine dose, number of doses, type of bait, use of adjuvants or route of administration.

Vaccination with an in vitro culture attenuated Babesia bovis strain safely protects highly susceptible adult cattle against acute bovine babesiosis.

Live in vivo attenuated Babesia bovis vaccines produced by sequential passages in splenectomized calves have historically been used to control acute bovine babesiosis in endemic areas worldwide. However, several constraints prevent the widespread use of these vaccines, including the need for several splenectomized calves to produce vaccine batches, and potential inconsistent parasite attenuation, which contraindicates their use for highly Babesia-susceptible adult cattle. Thus, the use of vaccines based on well-defined in vitro culture attenuated B. bovis strains emerges as a more sustainable and efficient alternative. Previous work demonstrated that the culture attenuated strain Att-S74-T3Bo is non-tick transmissible and able to safely protect calves against needle challenge with a B. bovis virulent strain. Herein we evaluated safety and efficacy of Att-S74-T3Bo in preventing acute babesiosis in adult (>1.5 year of age) cattle. Results demonstrated that Att-S74-T3Bo vaccination of adult animals (n=5) induced self-limiting signs of acute infection and protected the vaccinated animals against challenge with the homologous virulent B. bovis strain Vir-S74-T3Bo. Att-S74-T3Bo-vaccinated adult cattle developed significant (P<0.05) monocytosis, with concomitant neutropenia and CD4+ leukopenia, in peripheral blood early after vaccination. Also, vaccinated animals developed a specific signature of pro- and anti-inflammatory cytokine expression in peripheral blood and significant levels of IgM, total IgG, IgG1, and IgG2 against the B. bovis immunodominant antigen RAP-1 CT. Strikingly, none of the vaccinated animals showed any signs of acute babesiosis after challenge with Vir-S74-T3Bo. In contrast, control adult cattle (n=5) showed pathognomonic symptoms of acute babesiosis, and significant decrease (P<0.05) in lymphocytes, monocytes, and neutrophils, starting on day 7 post-challenge. All control animals developed severe acute disease and were euthanized on days 10 through 12 days post-challenge. Evidence from this study indicates that Att-S74-T3Bo safely protects highly susceptible adult cattle against challenge with a homologous virulent strain of B. bovis. In conclusion, Att-S74-T3Bo may be considered as a potential efficient and sustainable attenuated candidate vaccine strain to control acute bovine babesiosis in highly susceptible adult cattle. Future studies should focus on increasing the number of animals vaccinated, duration of immunity, and efficacy of this attenuated strain against heterologous virulent parasite strains.

Cutaneous Manifestations of Mycobacterium tuberculosis: A Literature Review.

Tuberculosis is an ancient disease that humanity struggled with for centuries and continues to struggle with. The bacteria Mycobacterium tuberculosis often infects the lungs through respiratory transmission and manifests itself through various symptoms, including cutaneous infections. Cutaneous tuberculosis (CTB) comprises about 1% to 1.5% of all extrapulmonary manifestations and is often accompanied by polymorphous lesions, including papules, nodules, plaques, ulcers, gummas, and verrucous lesions. CTB is most commonly observed in low-income, HIV, and immunosuppressed populations, similar to intrapulmonary manifestations. The main pathogen for CTB is M. tuberculosis but less commonly with M. bovis and BCG vaccine, and the modes of transmission are largely classified into exogenous and endogenous CTB. Current treatment options for CTB include oral therapy of antibiotic medications such as rifampicin, streptomycin, ethambutol, isoniazid, and pyrazinamide, which is occasionally combined with surgical intervention.

Intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis

Abstract Mucosal vaccines have the potential to elicit protective immune responses at the point of entry of respiratory pathogens thus preventing even the initial seed infection. Unlike licensed injectable vaccines, mucosal vaccines comprising protein subunits are only in the development stage. One of the primary challenges associated with mucosal vaccines has been the identification and characterization of safe yet effective mucosal adjuvants that can effectively prime multi-factorial mucosal immunity. In this study, we tested NanoSTING, a liposomal formulation of the endogenous activator of the stimulator of interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as a mucosal adjuvant. Intranasal administration of this vaccine provides protection comparable to subcutaneous administration of the live attenuated Mycobacterium bovis vaccine strain Bacille–Calmette–Guérin (BCG) upon challenge with aerosolized Mycobacterium tuberculosis Erdman strain. Protection against the bacterium is likely due to CXCR3+ lung resident T cells that are known to be important for the control of bacterial infection. Intranasal delivery also induces IFNγ secreting CD4+ T cells in lung which is necessary for intracellular bactericidal activity. Our results indicate that NanoSTING adjuvanted protein vaccines can elicit a multi-factorial immune response that provides durable protection from infection by M. tuberculosis.

A novel multi-component protein vaccine ECP001 containing a protein polypeptide antigen nPstS1 riching in T-cell epitopes showed good immunogenicity and protection in mice.

Tuberculosis (TB) is an infectious disease that seriously affects human health. Until now, the only anti-TB vaccine approved for use is the live attenuated Mycobacterium bovis (M. bovis) vaccine - BCG vaccine, but its protective efficacy is relatively low and does not provide satisfactory protection against TB in adults. Therefore, there is an urgent need for more effective vaccines to reduce the global TB epidemic. In this study, ESAT-6, CFP-10, two antigens full-length and the T-cell epitope polypeptide antigen of PstS1, named nPstS1, were selected to form one multi-component protein antigens, named ECP001, which include two types, one is a mixed protein antigen named ECP001m, the other is a fusion expression protein antigen named ECP001f, as candidates for protein subunit vaccines. were prepared by constructing one novel subunit vaccine by mixing or fusing the three proteins and combining them with aluminum hydroxide adjuvant, and the immunogenicity and protective properties of the vaccine was evaluated in mice. The results showed that ECP001 stimulated mice to produce high titre levels of IgG, IgG1 and IgG2a antibodies; meanwhile, high levels of IFN-γ and a broad range of specific cytokines were secreted by mouse splenocytes; in addition, ECP001 inhibited the proliferation of Mycobacterium tuberculosis in vitro with a capacity comparable to that of BCG. It can be concluded that ECP001 is a novel effective multicomponent subunit vaccine candidate with potential as BCG Initial Immunisation-ECP001 Booster Immunisation or therapeutic vaccine for M. tuberculosis infection.

Developing Anti-Babesia bovis Blood Stage Vaccines: A New Perspective Regarding Synthetic Vaccines

Bovine babesiosis is caused by the Apicomplexa parasites from the genus Babesia. It is one of the most important tick-borne veterinary diseases worldwide; Babesia bovis being the species associated with the most severe clinical signs of the disease and causing the greatest economic losses. Many limitations related to chemoprophylaxis and the acaricides control of transmitting vectors have led to the adoption of live attenuated vaccine immunisation against B. bovis as an alternative control strategy. However, whilst this strategy has been effective, several drawbacks related to its production have prompted research into alternative methodologies for producing vaccines. Classical approaches for developing anti-B. bovis vaccines are thus discussed in this review and are compared to a recent functional approach to highlight the latter's advantages when designing an effective synthetic vaccine targeting this parasite.

Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c

The vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) elicits an immune response that is protective against certain forms of tuberculosis (TB); however, because BCG efficacy is limited it is important to identify alternative TB vaccine candidates. Recently, the BCG deletion mutant and vaccine candidate BCGΔBCG1419c was demonstrated to survive longer in intravenously infected BALB/c mice due to enhanced biofilm formation, and better protected both BALB/c and C57BL/6 mice against TB-induced lung pathology during chronic stages of infection, relative to BCG controls. BCGΔBCG1419c-elicited protection also associated with lower levels of proinflammatory cytokines (i.e. IL6, TNFα) at the site of infection in C57BL/6 mice. Given the distinct immune profiles of BCG- and BCGΔBCG1419c-immunized mice during chronic TB, we set out to determine if there are early immunological events which distinguish these two groups, using multi-dimensional flow cytometric analysis of the lungs and other tissues soon after immunization. Our results demonstrate a number of innate and adaptive response differences between BCG- and BCGΔBCG1419c-immunized mice which are consistent with the latter being longer lasting and potentially less inflammatory, including lower frequencies of exhausted CD4+ T helper (TH) cells and higher frequencies of IL10-producing T cells, respectively. These studies suggest the use of BCGΔBCG1419c may be advantageous as an alternative TB vaccine candidate.

A Five Year Randomized Controlled Trial to Assess the Efficacy and Antibody Responses to a Commercial and Autogenous Vaccine for the Prevention of Infectious Bovine Keratoconjunctivitis.

A randomized control trial was performed over a five-year period to assess the efficacy and antibody response induced by autogenous and commercial vaccine formulations against infectious bovine keratoconjunctivitis (IBK). Calves were randomly assigned each year to one of three arms: an autogenous vaccine treatment that included Moraxella bovis (M. bovis), Moraxella bovoculi, and Mycoplasma bovoculi antigens, a commercial M. bovis vaccine treatment, or a sham vaccine treatment that consisted only of adjuvant. A total of 1198 calves were enrolled in the study. Calves were administered the respective vaccines approximately 21 days apart, just prior to turnout on summer pastures. Treatment effects were analyzed for IBK incidence, retreatment incidence, 205-day adjusted weaning weights, and antibody response to the type IV pilus protein (pili) of M. bovis as measured by a novel indirect enzyme-linked immunosorbent screening assay (ELISA). Calves vaccinated with the autogenous formulation experienced a decreased cumulative incidence of IBK over the entire study compared to those vaccinated with the commercial and sham formulations (24.5% vs. 30.06% vs. 30.3%, respectively, p = 0.25), and had less IBK cases that required retreatment compared to the commercial and sham formulations (21.4% vs. 27.9% vs. 34.3%, respectively, p = 0.15), but these differences were not significant. The autogenous formulation induced a significantly stronger antibody response than the commercial (p = 0.022) and sham formulations (p = 0.001), but antibody levels were not significantly correlated with IBK protection (p = 0.37).

CattleReview

Introduction: In this Cattle Review we consider three recent papers looking at postpartum uterine disease, Mycoplasma bovis and bovine respiratory disease vaccination.

Local Lung Immune Response to Mycobacterium bovis Challenge after BCG and M. bovis Heat-Inactivated Vaccination in European Badger (Meles meles).

Tuberculosis (TB) vaccination could be used as a key part of integrated strategies for the disease’s control if an effective and safe vaccine under field conditions is obtained. Recent studies in Spain have evaluated the protective efficacy of two oral vaccines against experimental challenge with live intra-bronchial Mycobacterium bovis in captive badgers: the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. With the objective of increasing the knowledge of the cellular development progress of infection and generating further tools to discriminate between mild and severe TB lesions between and within animals, the immunopathology of tuberculous lesions was studied to characterize the local immune response (cell type profile) within lung granulomas from control (non-vaccinated), BCG vaccinated and HIMB-vaccinated experimentally infected badgers with M. bovis. Four immunohistochemical protocols, for the specific detection of macrophages, T lymphocytes, B lymphocytes and plasma cells within TB granulomas in formalin fixed sections of the right middle lung lobe (lobe targeted for the M. bovis delivery), were performed. Immunolabelled sections were scanned and five randomly selected areas were analyzed with digital image analysis software. The results were expressed as the proportion of the positively immunolabelled area within the total area of the selected site. Data was analyzed using the statistical analysis software (SAS). In the three treatment groups, macrophages were the most abundant inflammatory cells within the granulomas, followed by B lymphocytes and plasma cells. T lymphocyes were absent in those granulomas. This would suggest a predominance of a non-specific innate response mediated by phagocytic cells over an adaptative humoral immune response. The proportion of macrophages and plasma cells was higher in BCG and HIMB-vaccinated badgers, respectively, suggesting the establishment of an adaptative humoral response in HIMB-vaccinated badgers. The lower bacterial load at the lung level, as well as the volume of lesions in lungs using magnetic resonance imaging in badgers with the HIMB vaccine in relation with local immune response presented, must be highlighted, since it would be an advantage in favor of its use under field conditions in terms of reducing TB transmission and environmental contamination.

BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny.

Vaccines have been traditionally developed with the presumption that they exert identical immunogenicity regardless of target population and that they provide protection solely against their target pathogen. However, it is increasingly appreciated that vaccines can have off-target effects and that vaccine immunogenicity can vary substantially with demographic factors such as age and sex. Bacille Calmette-Guérin (BCG), the live attenuated Mycobacterium bovis vaccine against tuberculosis (TB), represents a key example of these concepts. BCG vaccines are manufactured under different conditions across the globe generating divergent formulations. Epidemiologic studies have linked early life immunization with certain BCG formulations to an unanticipated reduction (∼50%) in all-cause mortality, especially in low birthweight males, greatly exceeding that attributable to TB prevention. This mortality benefit has been related to prevention of sepsis and respiratory infections suggesting that BCG induces “heterologous” protection against unrelated pathogens. Proposed mechanisms for heterologous protection include vaccine-induced immunometabolic shifts, epigenetic reprogramming of innate cell populations, and modulation of hematopoietic stem cell progenitors resulting in altered responses to subsequent stimuli, a phenomenon termed “trained immunity.” In addition to genetic differences, licensed BCG formulations differ markedly in content of viable mycobacteria key for innate immune activation, potentially contributing to differences in the ability of these diverse formulations to induce TB-specific and heterologous protection. BCG immunomodulatory properties have also sparked interest in its potential use to prevent or alleviate autoimmune and inflammatory diseases, including type 1 diabetes mellitus and multiple sclerosis. BCG can also serve as a model: nanoparticle vaccine formulations incorporating Toll-like receptor 8 agonists can mimic some of BCG’s innate immune activation, suggesting that aspects of BCG’s effects can be induced with non-replicating stimuli. Overall, BCG represents a paradigm for precision vaccinology, lessons from which will help inform next generation vaccines.

Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis.

In Europe, badgers (Meles meles) are recognized as major tuberculosis (TB) reservoir hosts with the potential to transmit infection to associated cattle herds. Recent studies in Spain have demonstrated that vaccination with a heat-inactivated Mycobacterium bovis vaccine (HIMB) successfully protects captive wild boar and red deer against progressive disease. The aim of this study was to evaluate the efficacy of two oral vaccines against TB in a badger model: the live-attenuated M. bovis bacillus Calmette-Guérin BCG vaccine (Danish strain) and a HIMB vaccine. Twenty-four badgers were separated in three treatment groups: oral vaccinated with live BCG (108 CFU, n = 5), oral vaccinated with HIMB (107 CFU, n = 7), and unvaccinated controls (n = 12). All badgers were experimentally infected with M. bovis (103 CFU) by the endobronchial route targeting the right middle lung lobe. Throughout the study, clinical, immunological, pathological, and bacteriological parameters of infection were measured. Both vaccines conferred protection against experimental TB in badger, as measured by a reduction of the severity and lesion volumes. Based on these data, HIMB vaccination appears to be a promising TB oral vaccine candidate for badgers in endemic countries.

Preliminary study on the effects of enrofloxacin, flunixin meglumine and pegbovigrastim on Mycoplasma bovis pneumonia

BackgroundMycoplasma bovis is a causative agent of disease in cattle causing many clinical conditions. Currently there are no commercial M. bovis vaccines in Europe and treatment is difficult with decreased antimicrobial susceptibility of M. bovis field isolates. Using an M. bovis calf infection model the effectiveness of enrofloxacin given alone; in combination with flunixin meglumine, a nonsteroidal anti-inflammatory drug; and a group with an additional treatment of pegbovigrastim, an immunostimulator, was evaluated.ResultsEnrofloxacin given alone stimulated a strong immune response, reduced the clinical manifestation and lung lessions of the M. bovis infection. In contrast the combination therapy appeared ineffective.ConclusionsIn this experiment enrofloxacin given alone appeared to be the most effective treatment of the M. bovis affected calves, whereas co-administration with flunixin meglumine, and pegbovigrastim was not beneficial in this trial.

Babesia bovis: Actualidad del desarrollo de una vacuna

Introducción. Babesia bovis es el principal agente causal de la babesiosis bovina, una importante enfermedad veterinaria transmitida por garrapatas a nivel mundial. Las estrategias convencionales para controlar esta parasitosis han presentado múltiples limitaciones por lo que el desarrollo de una vacuna basada en antígenos representa una estrategia apropiada para la prevención y el tratamiento. Objetivo. Describir los aspectos relevantes del ciclo de vida del parásito B. bovis, la epidemiología, diagnóstico y la aplicación de diferentes estrategias usadas para controlar esta parasitosis. Además, se discuten potenciales puntos de intervención para desarrollar una vacuna contra este parásito. Metodología. Se realizó una búsqueda en las bases de datos usando los términos: “Babesia bovis AND lyfe cycle”, “B. bovis vaccine and Vaccine candidates”, entre otras. Los estudios con mayor pertinencia publicados hasta la actualidad se revisaron completamente. Resultados: Los detalles de la biología de parásito B. bovis y el proceso molecular usado para ocasionar la enfermedad en el hospedador son poco conocidos, lo que explica que el desarrollado de estrategias para el control de esta parasitosis no hayan sido del todo eficientes. Por lo tanto, se requiere diseñar nuevas medidas, por ejemplo, desarrollar vacunas de nueva generación basadas en un enfoque funcional que permitan mejorar las condiciones de sanidad animal. Conclusiones. Comprender el complejo ciclo de vida de B. bovis permitirá estudiar las interacciones huésped-parásito-garrapata e identificar moléculas implicadas en la adhesión/invasión celular para evaluar su utilidad como componente de una vacuna que controle esta parasitosis.

Characterization of bovine γδ T cells phenotype following Mycobacterium bovis vaccination or virulent infection

Abstract Bovine tuberculosis caused by Mycobacterium bovis is a significant veterinary health problem. γδ T cells participate in the control of mycobacterial infections. Accumulating data suggest that mycobacterial infection regulates memory/effector phenotype and immune functions of mycobacterium-responsive γδ T cells. To date, the impact of both virulent M. bovis infection and Bacille Calmette-Guerin (BCG) vaccination on bovine γδ T cells memory/effector phenotype remains unknown. In this study, we addressed the functional and phenotypical differences in memory/activation marker, and chemokine receptor expression of M. bovis-specific γδ T cells following BCG vaccination or virulent M. bovis infection. Analysis of γδ T cells in blood, bronchoalveolar lavage fluid, and regional lymph nodes indicated that γδ T cells have phenotypic differences based on the expression of CD27 that suggest distinct functional properties. Here, we show that most peripheral γδ T cells display a CD27+ phenotype. Antigen recall responses showed that expression of CD27 correlates with the expansion of M. bovis-specific γδ T-cells. Thus, the CD27+ subset may comprise the adaptive γδ T cell compartment responding to virulent M. bovis infection and vaccination. Furthermore, we show that γδ T cells from neonatal calves are activated by aerosol BCG vaccination and adopt a lung-homing phenotype that is similar to that observed during virulent M. bovis infection, suggesting an important role for this T cell subset in the response to mucosal vaccination. The ability of γδ T cells to mount a robust local immune response supports the hypothesis that vaccine-elicited γδ T cell immunity might prove beneficial.