RESUMEN
Introduction: Babesia bovis, a tick-borne apicomplexan parasite causing bovine babesiosis, remains a significant threat worldwide, and improved and practical vaccines are needed. Previous studies defined the members of the rhoptry associated protein-1 (RAP-1), and the neutralization-sensitive rhoptry associated protein-1 related antigen (RRA) superfamily in B. bovis, as strong candidates for the development of subunit vaccines. Both RAP-1 and RRA share conservation of a group of 4 cysteines and amino acids motifs at the amino terminal end (NT) of these proteins. Methods and results: Sequence comparisons among the RRA sequences of several B. bovis strains and other Babesia spp parasites indicate a high level of conservation of a 15-amino acid (15-mer) motif located at the NT of the protein. BlastP searches indicate that the 15-mer motif is also present in adenylate cyclase, dynein, and other ATP binding proteins. AlphaFold2 structure predictions suggest partial exposure of the 15-mer on the surface of RRA of three distinct Babesia species. Antibodies in protected cattle recognize a synthetic peptide representing the 15-mer motif sequence in iELISA, and rabbit antibodies against the 15-mer react with the surface of free merozoites in immunofluorescence. Discussion and conclusion: The presence of the 15-mer-like regions in dynein and ATP-binding proteins provides a rationale for investigating possible functional roles for RRA. The demonstrated presence of a surface exposed B-cell epitope in the 15-mer motif of the B. bovis RRA, which is recognized by sera from protected bovines, supports its inclusion in future subunit epitope-based vaccines against B. bovis.
Asunto(s)
Antígenos de Protozoos , Babesia bovis , Babesiosis , Proteínas Protozoarias , Animales , Bovinos , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Babesia bovis/inmunología , Babesiosis/inmunología , Babesiosis/parasitología , Babesiosis/prevención & control , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/prevención & control , Secuencia Conservada , Epítopos de Linfocito B/inmunología , Proteínas Protozoarias/inmunología , Vacunas Antiprotozoos/inmunologíaAsunto(s)
Aminoquinolinas , Babesiosis , Quimioterapia Combinada , Humanos , Babesiosis/tratamiento farmacológico , Babesiosis/prevención & control , Aminoquinolinas/uso terapéutico , Aminoquinolinas/administración & dosificación , Animales , Antiprotozoarios/uso terapéutico , Antiprotozoarios/administración & dosificación , Erradicación de la Enfermedad/métodosRESUMEN
BACKGROUND: Babesia canis is a clinically relevant vector-borne pathogen in dogs, and its presence is expanding. The efficacy of Simparica Trio® (Zoetis) in the prevention of B. canis transmission was evaluated at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight. METHODS: Twenty-four (24) dogs were randomly allocated to either a placebo-treated group or one of two treatment groups with Simparica Trio. Dogs were infested with B. canis-infected Dermacentor reticulatus ticks 21 or 28 days after treatment administration. Blood samples for antibody and DNA detection were collected from each dog prior to tick infestation until 28 days after infestation. A dog was defined as being B. canis positive if it tested positive by both an indirect immunofluorescence assay (IFA) and PCR at any time during the study. RESULTS: No treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFA and PCR. None of the Simparica Trio-treated animals displayed any clinical symptoms or tested positive, resulting in a 100% efficacy in the prevention of canine babesiosis (P < 0.0001). CONCLUSIONS: A single treatment with Simparica Trio at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight prevents the transmission of B. canis by infected D. reticulatus to dogs for at least 28 days.
Asunto(s)
Acaricidas , Babesia , Babesiosis , Enfermedades de los Perros , Animales , Perros , Acaricidas/uso terapéutico , Administración Oral , Azetidinas , Babesia/genética , Babesiosis/prevención & control , Dermacentor , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/prevención & control , Macrólidos , Pirantel/uso terapéutico , Compuestos de Espiro , Infestaciones por Garrapatas/tratamiento farmacológico , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinariaRESUMEN
Babesiosis is a parasitic disease caused by intraerythrocytic parasites of the genus Babesia, which infect both wild and domestic animals. Merozoite surface antigens (MSAs) have been identified as efficient immunogens in Babesia-infected animals. MSAs play a key role in the invasion process and have been proposed as potential targets for vaccine development. Epitope-based vaccines offer several advantages over whole protein vaccines as the immunogenic proteins are small and can induce both Th1 and Th2 immune responses, which are desirable for protection. However, the MSA, particularly gp45, is polymorphic in Babesia bigemina, posing a challenge to vaccine development. The purpose of this study was to develop a recombinant gpME (gp45-multi-epitope) for a vaccine against Babesia bigemina. B-cell, T-cell, and HLA epitope predictions were used to synthesize the gpME sequence from the consensus sequence of gp45. The gpME sequence was synthesized and cloned in the pET28α vector through the commercial biotechnology company to get pET28-gpME. The plasmid cloned with the gpME sequence comprising 1068 bp was expressed in a bacterial expression system. A band of 39 kDa of rec-gpME was obtained via SDS-PAGE and Western blotting. Rec-gpME @200ng was injected in calves 3 times at 2 weeks interval. The humoral response was evaluated through the indirect ELISA method. The ELISA with rec-gp45 protein showed a significant value of optical density. The recombinant protein containing multiple epitopes from the MSA gp45 may represent a promising candidate for a vaccine against Babesia bigemina.
Asunto(s)
Babesia , Babesiosis , Enfermedades de los Bovinos , Animales , Bovinos , Antígenos de Superficie , Epítopos , Merozoítos , Babesiosis/prevención & control , Enfermedades de los Bovinos/prevención & controlRESUMEN
BACKGROUND: The protozoan parasite Babesia microti that causes the zoonotic disease babesiosis resides in the erythrocytes of its mammalian host during its life-cycle. No effective vaccines are currently available to prevent Babesia microti infections. METHODS: We previously identified a highly seroactive antigen, named Bm8, as a B. microti conserved erythrocyte membrane-associated antigen, by high-throughput protein chip screening. Bioinformatic and phylogenetic analysis showed that this membrane-associated protein is conserved among apicomplexan hemoprotozoa, such as members of genera Babesia, Plasmodium and Theileria. We obtained the recombinant protein Bm8 (rBm8) by prokaryotic expression and purification. RESULTS: Immunofluorescence assays confirmed that Bm8 and its Plasmodium homolog were principally localized in the cytoplasm of the parasite. rBm8 protein was specifically recognized by the sera of mice infected with B. microti or P. berghei. Also, mice immunized with Bm8 polypeptide had a decreased parasite burden after B. microti or P. berghei infection. CONCLUSIONS: Passive immunization with Bm8 antisera could protect mice against B. microti or P. berghei infection to a certain extent. These results lead us to hypothesize that the B. microti conserved erythrocyte membrane-associated protein Bm8 could serve as a novel broad-spectrum parasite vaccine candidate since it elicits a protective immune response against Babesiosis and Plasmodium infection.
Asunto(s)
Babesia microti , Babesia , Babesiosis , Gastrópodos , Malaria , Animales , Ratones , Babesia microti/genética , Babesiosis/prevención & control , Filogenia , Proteínas de la Membrana , MamíferosRESUMEN
The apicomplexan tickborne parasites Babesia bovis and B. bigemina are the major causative agents of bovine babesiosis, a disease that negatively affects the cattle industry and food safety around the world. The absence of correlates of protection represents one major impediment for the development of effective and sustainable vaccines against bovine babesiosis. Herein we superinfected cattle with attenuated and virulent strains of B. bovis to investigate immune correlates of protection against acute bovine babesiosis. Three 6-month-old Holstein calves were infected intravenously (IV) with the in vitro culture attenuated Att-S74-T3Bo B. bovis strain (106 infected bovine red blood cells (iRBC)/calf) while three age-matched Holstein calves were inoculated IV with normal RBC as controls (106 RBC/calf). All Att-S74-T3Bo-infected calves showed a significant increase in temperature early after inoculation but recovered without treatment. Att-S74-T3Bo-infected calves also developed: (a) monocytosis, neutropenia, and CD4+ lymphopenia in peripheral blood on days 3 to 7 post-inoculation; (b) significant levels of TNFα, CXCL10, IFNγ, IL-4, and IL-10 in sera at day 6 after infection; and (c) IgM and IgG against B. bovis antigens, starting at days 10 and 30 post-inoculation, respectively. At 46 days post-Att-S74-T3Bo inoculation, all experimental calves were infected IV with the homologous virulent B. bovis strain Vir-S74-T3Bo (107 iRBC/calf). All Att-S74-T3Bo-infected calves survived superinfection with Vir-S74-T3Bo without displaying signs of acute babesiosis. In contrast, control animals showed signs of acute disease, starting at day 10 post-Vir-S74-T3Bo infection, and two of them were humanely euthanized at days 13 and 14 after inoculation due to the severity of their symptoms. Also, control calves showed higher (P<0.05) parasite load in peripheral blood compared to animals previously exposed to Att-S74-T3Bo. No significant alterations in the profile of leukocytes and cytokines were observed in Att-S74-T3Bo-inoculated after Vir-S74-T3Bo infection. In conclusion, data demonstrate novel changes in the profile of blood immune cells and cytokine expression in peripheral blood that are associated with protection against acute bovine babesiosis. These identified immune correlates of protection may be useful for designing effective and sustainable vaccines against babesiosis in cattle.
Asunto(s)
Babesia bovis , Babesiosis , Antígenos de Grupos Sanguíneos , Neutropenia , Bovinos , Animales , Babesiosis/prevención & control , Vacunación , CitocinasRESUMEN
Babesiosis is a tick-borne disease caused by intraerythrocytic Babesia parasites. It is a well-known illness in companion animals and livestock, resulting in substantial economic losses in the cattle industry. Babesiosis is also recognized as an emerging zoonosis of humans in many countries worldwide. There is no vaccine against human babesiosis. Currently, preventive measures are focused on vector avoidance. Although not always effective, treatment includes antimicrobial therapy and exchange transfusion. In this review, we discuss the host's immune response to the parasite, vaccines being used to prevent babesiosis in animals, and lessons from malaria vaccine development efforts to inform the development of a human babesiosis vaccine. An effective human vaccine would be a significant advance towards curtailing this rapidly emerging disease.
Asunto(s)
Babesia , Babesiosis , Enfermedades de los Bovinos , Enfermedades por Picaduras de Garrapatas , Vacunas , Animales , Babesiosis/parasitología , Babesiosis/prevención & control , Bovinos , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/prevención & control , Estudios de Factibilidad , HumanosRESUMEN
Canine babesiosis is an important tick-borne disease worldwide. The prevalence varies between regions and countries; however, the incidence of tick infection is associated with the status of preventive tick control measures by the owner. To date, no studies have investigated the incidence of canine babesiosis and the condition of tick prevention in Taiwan. Therefore, the true risk of babesiosis could be underestimated in dogs that are not receiving tick prophylaxis. Samples were collected at 51 hospitals around Taiwan from 265 dogs not receiving regular tick prophylaxis. Diagnostic real-time PCR was performed, and 28 dogs (10.6%) were positive for Babesia spp., including B. gibsoni (26/28) and B. vogeli (2/28). Thirty-nine dogs (14.7%) were seropositive to B. gibsoni. Take the real-time PCR positive as the Babesia infected case, the positive and negative predictive value of serological assay were 64.1% and 98.7%, respectively. The seropositivity of B. gibsoni was significantly associated with real-time PCR positivity for Babesia spp. and vice versa (p < 0.001). The odds of seropositive representing real-time PCR positivity was 132.7 times greater than the seronegative (OR: 132.731, 95% CI 35.683-493.728). Risk factors in the population identified included: dogs with a short-haired coat; intact dogs; dogs from multi-dog households; dogs with more than 10 ticks and fleas on the skin; dogs that go outdoors more than 9 times per week; and dogs with an abnormal blood test result that included anemia, thrombocytopenia, and leukopenia. However, the dogs were not tested for other co-infections, therefore, these hematological risk factors should be carefully interpreted and confirmed by further diagnostic tests. In conclusion, when dogs present with abnormal blood test results and share the risk factors listed above, babesiosis should be seriously considered and followed up with molecular and serological testing. The serological assay used in this study can provide valuable information in diagnosing babesiosis in dogs in Taiwan.
Asunto(s)
Babesia , Babesiosis , Enfermedades de los Perros , Garrapatas , Animales , Babesia/genética , Babesiosis/diagnóstico , Babesiosis/epidemiología , Babesiosis/prevención & control , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/prevención & control , Perros , Taiwán/epidemiologíaRESUMEN
INTRODUCTION: Equine granulocytic anaplasmosis (EGA) and equine piroplasmosis (EP) are triggered by tick-borne pathogens - the intracellular bacterium Anaplasma phagocytophilum and the intracellular protozoa Babesia caballi and Theileria equi. These pathogens attack cells in the blood stream and cause similar clinical symptoms and changes in laboratory values. Although the treatment principles are naturally different, similarities in prophylaxis exists due to the transmission route. Tick transmitted pathogens can play a greater role in equine medicine in the future due to various factors, such as the tendency of relevant tick species to spread, but also the increasing import and travel activities of and with pets (both in the context of sporting events and as a leisure activity). While EGA is endemic in Central Europe, EP is a sporadic disease in Switzerland, Austria and Germany. However, EP must be viewed as underdiagnosed, as horses persistently infected with T. equi are also repeatedly detected in Central Europe. These diseases should be considered in horses with a fever and corresponding laboratory changes. Available diagnostic tests are direct pathogen detection by blood smear or PCR, and, indirect antibody detection, which is considered to be highly sensitive and (as a competitive ELISA) also very specific. Acute infections can be detected with PCR, serology is more suitable for chronic infections. A pathogen-free condition after treatment can be demonstrated with decreasing antibody titers in combination with repeated PCR tests. In addition, clinically healthy horses infected with T. equi should be identified by antibody detection and appropriate preventative transmission measures must be initiated. The prophylaxis of tick bites in horses is difficult due to the high exposure, and long-term tick bite prevention can hardly be guaranteed. Monitoring of tick activity and strict measures to prevent the spread of the pathogen within the tick population are therefore of great importance.
INTRODUCTION: L'anaplasmose granulocytaire équine (EGA) et la piroplasmose équine (EP) sont causées par des agents pathogènes transmis par les tiques la bactérie intracellulaire Anaplasma phagocytophilum et les protozoaires intracellulaires Babesia caballi et Theileria equi. Ces agents pathogènes attaquent les cellules sanguines et provoquent des symptômes cliniques similaires et des modifications des valeurs de laboratoire. Bien que les principes de traitement soient naturellement différents, des similitudes dans la prophylaxie existent en raison de la voie de transmission. Les agents pathogènes transmis par les tiques pourraient jouer un rôle plus important en médecine équine à l>avenir en raison de divers facteurs, tels que la tendance des espèces de tiques concernées à se propager, mais aussi l>augmentation des activités d>importation et de voyage d>animaux de compagnie avec eux (à la fois dans le contexte d>événements sportifs et comme activité de loisir). Alors que l>EGA est endémique en Europe centrale, l>EP est une maladie sporadique en Suisse, en Autriche et en Allemagne. Cependant, l'EP doit être considérée comme sous-diagnostiquée, car des chevaux infectés de manière persistante par T. equi ont également été détectés à plusieurs reprises en Europe centrale. Ces maladies doivent être envisagées chez les chevaux présentant de la fièvre et des modifications biologiques correspondantes. Les tests de diagnostic disponibles sont la détection directe des agents pathogènes par frottis sanguin ou par PCR et la détection indirecte des anticorps, qui est considérée comme très sensible et, en tant qu'ELISA compétitif, également très spécifique. Les infections aiguës peuvent être détectées par PCR, la sérologie est plus adaptée aux infections chroniques. Une condition sans agent pathogène après le traitement peut être démontrée avec des titres d'anticorps décroissants en combinaison avec des tests PCR répétés. De plus, les chevaux cliniquement sains infectés par T. equi doivent être identifiés par détection d'anticorps et des mesures appropriées pour prévenir la transmission doivent être initiées. La prophylaxie des morsures de tiques chez les chevaux est difficile en raison de la forte exposition et la prévention des morsures de tiques à long terme peut difficilement être garantie. La surveillance de l'activité des tiques et des mesures strictes pour empêcher la propagation de l'agent pathogène au sein de la population de tiques sont donc d'une grande importance.
Asunto(s)
Anaplasmosis , Babesiosis , Enfermedades de los Caballos , Anaplasmosis/diagnóstico , Anaplasmosis/epidemiología , Anaplasmosis/prevención & control , Animales , Austria/epidemiología , Babesiosis/diagnóstico , Babesiosis/epidemiología , Babesiosis/prevención & control , Alemania/epidemiología , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/prevención & control , Caballos , Infección Persistente/veterinaria , Suiza/epidemiologíaRESUMEN
Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis, proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro: P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN-) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis.
Asunto(s)
Babesia bovis , Babesiosis , Enfermedades de los Bovinos , Animales , Anticuerpos Neutralizantes , Antígenos de Protozoos , Babesiosis/prevención & control , Bovinos , Epítopos de Linfocito T , Inmunidad Humoral , Proteínas ProtozoariasRESUMEN
Babesia gibsoni is a tick-transmitted intraerythrocytic apicomplexan parasite that causes babesiosis in dogs. Due to the strong side effects and lack of efficacy of current drugs, novel drugs against B. gibsoni are urgently needed. Natural products as a source for new drugs is a good choice for screening drugs against B. gibsoni. The current study focuses on identifying novel potential drugs from natural products against B. gibsoniin vitro. Parasite inhibition was verified using a SYBR green I-based fluorescence assay. A total of 502 natural product compounds were screened for anti-B. gibsoni activity in vitro. Twenty-four compounds showed high growth inhibition (>80%) on B. gibsoni and 5 plant-derived compounds were selected for further study. The half-maximal inhibitory concentration (IC50) values of lycorine (LY), vincristine sulfate (VS), emetine·2HCl (EME), harringtonine (HT) and cephaeline·HBr (CEP) were 784.4 ± 3.3, 643.0 ± 2.8, 253.1 ± 1.4, 23.4 ± 1.2, and 108.1 ± 4.3 nM, respectively. The Madin-Darby canine kidney (MDCK) cell line was used to assess cytotoxicity of hit compounds. All compounds showed minimal toxicity to the MDCK cells. The effects of hit compounds combined with diminazene aceturate (DA) on B. gibsoni were further evaluated in vitro. VS, EME, HT or CEP combined with DA showed synergistic effects against B. gibsoni, whereas LY combined with DA showed an antagonistic effect against B. gibsoni. The results obtained in this study indicate that LY, VS, EME, HT and CEP are promising compounds for B. gibsoni treatment.
Asunto(s)
Antiprotozoarios/farmacología , Babesia/efectos de los fármacos , Productos Biológicos/farmacología , Diminazeno/análogos & derivados , Animales , Babesiosis/parasitología , Babesiosis/prevención & control , Diminazeno/farmacología , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/prevención & control , Perros , Evaluación Preclínica de Medicamentos , Concentración 50 InhibidoraRESUMEN
An effective strategy to control blood-borne diseases and prevent outbreak recrudescence involves targeting conserved metabolic processes that are essential for pathogen viability. One such target for Plasmodium and Babesia, the infectious agents of malaria and babesiosis, respectively, is the mitochondrial cytochrome bc1 protein complex, which can be inhibited by endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogen Babesia duncani to evaluate the structure-activity relationship, safety, efficacy, and mode of action of ELQs. We identified a potent and highly selective ELQ prodrug (ELQ-502), which, alone or in combination with atovaquone, eliminates B. microti and B. duncani infections in vitro and in mouse models of parasitemia and lethal infection. The strong efficacy at low dose, excellent safety, bioavailability, and long half-life of this experimental therapy make it an ideal clinical candidate for the treatment of human infections caused by Babesia and its closely related apicomplexan parasites.
Asunto(s)
Babesia , Babesiosis , Animales , Atovacuona/farmacología , Babesiosis/tratamiento farmacológico , Babesiosis/prevención & control , Citocromos , Ratones , Parasitemia/tratamiento farmacológicoRESUMEN
BACKGROUND: Cattle fever ticks (CFT), Rhipicephalus (Boophilus) annulatus and R. (B.) microplus, are vectors of microbes causing bovine babesiosis and pose a threat to the economic viability of the US livestock industry. Efforts by the Cattle Fever Tick Eradication Program (CFTEP) along the US-Mexico border in south Texas are complicated by the involvement of alternate hosts, including white-tailed deer (Odocoileus virginianus) and nilgai (Boselaphus tragocamelus). METHODS: In the present study, we use a spatially explicit, individual-based model to explore the potential effects of host species composition and host habitat use patterns on southern cattle fever ticks (SCFT, R. (B.) microplus) infestation dynamics and efficacy of eradication schemes. RESULTS: In simulations without eradication efforts, mean off-host larval densities were much higher when cattle were present than when only white-tailed deer and nilgai were present. Densities in mesquite and meadows were slightly higher, and densities in mixed brush were much lower, than landscape-level densities in each of these scenarios. In eradication simulations, reductions in mean off-host larval densities at the landscape level were much smaller when acaricide was applied to cattle only, or to cattle and white-tailed deer, than when applied to cattle and nilgai. Relative density reductions in mesquite, mixed brush, and meadows depended on host habitat use preferences. Shifting nilgai habitat use preferences increasingly toward mixed brush and away from mesquite did not change mean off-host larval tick densities noticeably at the landscape level. However, mean densities were increased markedly in mesquite and decreased markedly in mixed brush, while no noticeable change in density was observed in meadows. CONCLUSIONS: Our results suggest that continued integration of field data into spatially explicit, individual-based models will facilitate the development of novel eradication strategies and will allow near-real-time infestation forecasts as an aid in anticipating and preventing wildlife-mediated impacts on SCFT eradication efforts.
Asunto(s)
Dinámica Poblacional/estadística & datos numéricos , Rhipicephalus , Infestaciones por Garrapatas/veterinaria , Anaplasmosis/prevención & control , Animales , Animales Salvajes/parasitología , Antílopes/parasitología , Vectores Artrópodos , Babesiosis/prevención & control , Bovinos , Enfermedades de los Bovinos/prevención & control , Simulación por Computador/estadística & datos numéricos , Ciervos/parasitología , Reservorios de Enfermedades/veterinaria , Interacciones Huésped-Parásitos , Ganado/parasitología , México , Texas , Control de Ácaros y Garrapatas/métodosRESUMEN
Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.
Asunto(s)
Babesia microti/inmunología , Babesiosis/inmunología , Babesiosis/prevención & control , Evaluación Preclínica de Medicamentos , Parasitemia/inmunología , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico , Animales , Anticuerpos Antiprotozoarios/sangre , Linfocitos B/inmunología , Babesiosis/parasitología , Sistemas de Liberación de Medicamentos/métodos , Femenino , Humanos , Inmunidad , Liposomas/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones SCID , Parasitemia/terapia , Linfocitopenia-T Idiopática CD4-Positiva/inmunología , Garrapatas/parasitologíaRESUMEN
BACKGROUND: Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicity of the 6cys proteins in the related Plasmodium parasites required the identification of transmission blocking domains in these molecules for vaccine design. Hereby, the immunogenic efficacy of recombinant (r) B. bovis 6cys A and B proteins as a TBV formulation was studied. METHODS: The immunogenicity of r6cys A and 6cys B proteins expressed in a eukaryotic system was evaluated in a cattle immunization trial (3 immunized and 3 control calves). A B. bovis sexual stage induction in vitro inhibition assay to assess the ability of antibodies to block the production of sexual forms by the parasite was developed. RESULTS: Immunized cattle generated antibodies against r6cys A and r6cys B that were unable to block sexual reproduction of the parasite in ticks. Additionally, these antibodies also failed in recognizing native 6cys A and 6cys B and peptides representing 6cys A and 6cys B functional domains and in inhibiting the development of sexual forms in an in vitro induction system. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of 6cys A and 6cys B recognized recombinant and native forms of both 6cys proteins as well as peptides representing 6cys A and 6cys B functional domains and were able to neutralize development of sexual forms of the parasite in vitro. CONCLUSIONS: These data, combined with similar work performed on Plasmodium 6cys proteins, indicate that an effective 6cys protein-based TBV against B. bovis will require identifying and targeting selected regions of proteins containing epitopes able to reduce transmission.
Asunto(s)
Babesia bovis/inmunología , Babesiosis/prevención & control , Enfermedades de los Bovinos/prevención & control , Proteínas Protozoarias/inmunología , Vacunas Antiprotozoos/inmunología , Animales , Anticuerpos Antiprotozoarios/inmunología , Babesia bovis/genética , Babesia bovis/fisiología , Babesiosis/inmunología , Babesiosis/parasitología , Babesiosis/transmisión , Bovinos , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/transmisión , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Proteínas Protozoarias/administración & dosificación , Proteínas Protozoarias/genética , Vacunas Antiprotozoos/administración & dosificación , Vacunas Antiprotozoos/genética , Conejos , Reproducción , Rhipicephalus/parasitología , Rhipicephalus/fisiologíaRESUMEN
Babesia microti is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the neck of the rhoptry and studies indicate that these proteins play an important role in the process of red blood cell invasion. In the present study, we report on the bioinformatic analysis, cloning, and recombinant gene expression of two truncated rhoptry neck proteins 2 (BmRON2), as well as their potential for incorporation in a candidate vaccine for babesiosis. Western blot and immunofluorescence antibody (IFA) assays were performed to detect the presence of specific antibodies against BmRON2 in infected mice and the localization of N-BmRON2 in B. microti parasites. In vitro experiments were carried out to investigate the role of BmRON2 proteins during the B. microti invasion process and in vivo experiments to investigate immunoprotection. Homologous sequence alignment and molecular phylogenetic analysis indicated that BmRON2 showed similarities with RON2 proteins of other Babesia species. We expressed the truncated N-terminal (33-336 aa, designated rN-BmRON2) and C-terminal (915-1171 aa, designated rC-BmRON2) fragments of the BmRON2 protein, with molecular weights of 70 and 29 kDa, respectively. Western blot assays showed that the native BmRON2 protein is approximately 170 kDa, and that rN-BmRON2 was recognized by serum of mice experimentally infected with B. microti. Immunofluorescence analysis indicated that the BmRON2 protein was located at the apical end of merozoites, at the opposite end of the nucleus. In vitro red blood cell invasion inhibition studies with B. microti rBmRON2 proteins showed that relative invasion rate of rN-BmRON2 and rC-BmRON2 group is 45 and 56%, respectively. Analysis of the host immune response after immunization and B. microti infection showed that both rN-BmRON2 and rC-BmRON2 enhanced the immune response, but that rN-BmRON2 conferred better protection than rC-BmRON2. In conclusion, our results indicate that truncated rhoptry neck protein 2, especially its N-terminal fragment (rN-BmRON2), plays an important role in the invasion of host red blood cells, confers immune protection, and shows good potential as a candidate vaccine against babesiosis.
Asunto(s)
Antígenos de Protozoos/inmunología , Babesia microti/inmunología , Babesiosis/prevención & control , Interacciones Huésped-Parásitos/inmunología , Proteínas Protozoarias/inmunología , Vacunas Antiprotozoos/inmunología , Animales , Antígenos de Protozoos/genética , Babesia microti/genética , Modelos Animales de Enfermedad , Eritrocitos/inmunología , Eritrocitos/parasitología , Técnica del Anticuerpo Fluorescente , Expresión Génica , Inmunización , Ratones , Filogenia , Transporte de Proteínas , Proteínas Protozoarias/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunologíaRESUMEN
Cattle tick fever (CTF) causes significant economic losses in the livestock sector. The pathogenic action of the hemoparasites is associated with anemia, weight loss, abortion and reduced productivity, which result with animal death. Programs to prevent CTF involve several procedures, including immunization, chemoprophylaxis and use of ectoparasiticides, together with the vector control in the environment. The objective of this study was to report an acute outbreak of CTF in a group of 157 Hereford cattle from a farm without presence of the vector, that were moved to a farm in the same state with a high tick infestation (Rhipicephalus microplus). On the day before the transportation, the animals received a chemoprophylaxis with imidocarb dipropionate (3 mg/kg, SC), which was repeated 21 days after the first application. After 42 days, some animals showed signs compatible with CTF, which was confirmed through clinical examination, necropsy, histopathological and hemoparasitological analyses. The morbidity rate was 37.6% and the mortality rate was 24.8%. Calves that were recently weaned were the group most affected with the tick fever, morbidity (100% and mortality (73%). Chemoprophylaxis in association with use of ectoparasiticides was not sufficient to control the outbreak of the disease.
Asunto(s)
Anaplasmosis , Babesiosis , Enfermedades de los Bovinos , Quimioprevención/veterinaria , Infestaciones por Garrapatas , Anaplasmosis/diagnóstico , Anaplasmosis/epidemiología , Anaplasmosis/prevención & control , Animales , Babesiosis/diagnóstico , Babesiosis/epidemiología , Babesiosis/prevención & control , Bovinos , Enfermedades de los Bovinos/prevención & control , Rhipicephalus , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinariaRESUMEN
Babesiosis is a tick-borne disease that may be deadly under certain conditions. Occupational health nurses should teach workers about the disease and the importance of prevention strategies.
Asunto(s)
Babesiosis/prevención & control , Exposición Profesional/prevención & control , Animales , Babesia , Babesiosis/diagnóstico , Babesiosis/tratamiento farmacológico , Babesiosis/transmisión , Humanos , Ixodes/parasitología , Enfermería del Trabajo/métodos , Enfermedades por Picaduras de Garrapatas/prevención & controlRESUMEN
Two people in the UK have recently fallen ill with rare tickborne infections, as Josh Loeb reports.