Mario Canales

A ten-year review of commercial vaccine performance for control of tick infestations on cattle.

Abstract Ticks are important ectoparasites of domestic and wild animals, and tick infestations economically impact cattle production worldwide. Control of cattle tick infestations has been primarily by application of acaricides which has resulted in selection of resistant ticks and environmental pollution. Herein we discuss data from tick vaccine application in Australia, Cuba, Mexico and other Latin American countries. Commercial tick vaccines for cattle based on the Boophilus microplus Bm86 gut antigen have proven to be a feasible tick control method that offers a cost-effective, environmentally friendly alternative to the use of acaricides. Commercial tick vaccines reduced tick infestations on cattle and the intensity of acaricide usage, as well as increasing animal production and reducing transmission of some tick-borne pathogens. Although commercialization of tick vaccines has been difficult owing to previous constraints of antigen discovery, the expense of testing vaccines in cattle, and company restructuring, the success of these vaccines over the past decade has clearly demonstrated their potential as an improved method of tick control for cattle. Development of improved vaccines in the future will be greatly enhanced by new and efficient molecular technologies for antigen discovery and the urgent need for a tick control method to reduce or replace the use of acaricides, especially in regions where extensive tick resistance has occurred.

Field studies and cost-effectiveness analysis of vaccination with Gavac against the cattle tick boophilus microplus

The control of tick infestations and the transmission of tick-borne diseases remains a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant Boophilus microplus gut antigen Bm86 have been developed. These vaccines have been shown to control tick infestations in the field. However, extensive field studies investigating the efficacy and cost-effectiveness of vaccination have not been reported and are needed to appraise the effect of this new approach for tick control. Here is reported the results of the application of Gavac in a field trial including more than 260,000 animals in Cuba. In this study the correlation between the antibody response to vaccination and the effect on ticks fertility is determined. Physiological status of the animals was found to affect the primary response to vaccination but not the antibody titers after revaccination. A cost-effectiveness analysis showed a 60% reduction in the number acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of

Control of ticks resistant to immunization with Bm86 in cattle vaccinated with the recombinant antigen Bm95 isolated from the cattle tick, Boophilus microplus.

23.4 animal-1 year-1. These results clearly demonstrate the advantage of vaccination and support the application of Gavac for tick control.

Large-scale production in Pichia pastoris of the recombinant vaccine Gavac™ against cattle tick

The recombinant Bm86-containing vaccine Gavac(TM) against the cattle tick Boophilus microplus has proved its efficacy in a number of experiments, especially when combined with acaricides in an integrated manner. However, tick isolates such as the Argentinean strain A, show low susceptibility to this vaccine. In this paper we report on the isolation of the Bm95 gene from the B. microplus strain A, which was cloned and expressed in the yeast Pichia pastoris producing a glycosylated and particulated recombinant protein. This new antigen was effective against different tick strains in a pen trial, including the B. microplus strain A, resistant to vaccination with Bm86. A Bm95-based vaccine was used to protect cattle against tick infestations under production conditions, lowering the number of ticks on vaccinated animals and, therefore, reducing the frequency of acaricide treatments. The Bm95 antigen from strain A was able to protect against infestations with Bm86-sensitive and Bm86-resistant tick strains, thus suggesting that Bm95 could be a more universal antigen to protect cattle against infestations by B. microplus strains from different geographical areas.

VACCINATION AGAINST TICKS (BOOPHILUS SPP.) : THE EXPERIENCE WITH THE BM86-BASED VACCINE GAVAC

A gene coding for the Bm86 tick protein was recently cloned, expressed in Pichia pastoris and shown to induce an inmunological response in cattle against ticks. Moreover, the Gavac vaccine (Heber Biotec S.A., Havana, Cuba), which contains this recombinant protein, has proved to control the Boophilus microplus populations under field conditions. This paper reviews the development and large-scale production of this vaccine, the efficacy of the resulting product and the strategy followed in designing its production plant. The production plant fulfills biosafety requirements and GMP.

Identification and characterization of Rhipicephalus (Boophilus) microplus candidate protective antigens for the control of cattle tick infestations.

The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant B. microplus gut antigen Bm86 have been developed. Our vaccine formulation (Gavac, Heber Biotec S.A., Havana, Cuba) has been registered and is commercially available in Cuba, Colombia, Dominican Republic, Brazil and Mexico. In controlled pen trials, Gavac has been effective for the control of artificial infestations of B. annulatus, B. decoloratus and chemical-sensitive and resistant B. microplus strains from Australia, Africa, America and Iran. In controlled field trials in Cuba, Brazil, Argentina and Mexico, Gavac has shown a 55-100% efficacy in the control of B. microplus infestations in grazing cattle 12-36 weeks after the first vaccination. Field trials under production conditions have been conducted in Cuba, Colombia, Brazil and Mexico in pure and cross-bred cattle herds. The application of Gavac has increased the time between acaricide treatments by an average of 32 /-21 days (P = 0.0005) resulting in important savings for the cattle industry. In Cuba, a cost-effectiveness analysis was conducted in more than 260000 animals. The cost-effectiveness analysis showed a 60% reduction in the number of acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of 23.4 dollars animal(-1) year (-1). These results clearly demonstrate the advantage of vaccination and support the application of Gavac for the control of Boophilus spp. infestations.

Control of Boophilus microplus populations in grazing cattle vaccinated with a recombinant Bm86 antigen preparation

The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Tick vaccines constitute a cost-effective and environmentally friendly alternative to tick control. The recombinant Rhipicephalus microplus Bm86 antigen has been shown to protect cattle against tick infestations. However, variable efficacy of Bm86-based vaccines against geographic tick strains has encouraged the research for additional tick-protective antigens. Herein, we describe the analysis of R. microplus glutathione-S transferase, ubiquitin (UBQ), selenoprotein W, elongation factor-1 alpha, and subolesin (SUB) complementary DNAs (cDNAs) by RNA interference (RNAi) in R. microplus and Rhipicephalus annulatus. Candidate protective antigens were selected for vaccination experiments based on the effect of gene knockdown on tick mortality, feeding, and fertility. Two cDNA clones encoding for UBQ and SUB were used for cattle vaccination and infestation with R. microplus and R. annulatus. Control groups were immunized with recombinant Bm86 or adjuvant/saline. The highest vaccine efficacy for the control of tick infestations was obtained for Bm86. Although with low immunogenic response, the results with the SUB vaccine encourage further investigations on the use of recombinant subolesin alone or in combination with other antigens for the control of cattle tick infestations. The UBQ peptide showed low immunogenicity, and the results of the vaccination trial were inconclusive to assess the protective efficacy of this antigen. These experiments showed that RNAi could be used for the selection of candidate tick-protective antigens. However, vaccination trials are necessary to evaluate the effect of recombinant antigens in the control of tick infestations, a process that requires efficient recombinant protein production and formulation systems.

Targeting arthropod subolesin/akirin for the development of a universal vaccine for control of vector infestations and pathogen transmission.

Current methods for the control of cattle tick Boophilus microplus infestations are not effective and the parasite remains a serious problem for the cattle industry in tropical and subtropical areas. Recently, we developed a vaccine against B. microplus employing a recombinant Bm86 (rBm86) antigen preparation (Gavac, Heber Biotec) and it was shown to induce a protective response in vaccinated animals under controlled conditions. Here we show that, under field conditions in grazing cattle, the vaccine is able to control B. microplus populations. Two parasite-free farms were employed for the study. In the first farm, animals were vaccinated with the recombinant vaccine, while, in the second, animals received a saline injection in adjuvant. After immunization, animals were artificially infected and the infestation rate was recorded. Over the 33 weeks of the experiment, the infestation rate was lower in the vaccinated group compared with the control group. At the end of the experiment it was necessary to use chemicals in the control farm after serious losses in production and animals.

Vaccination with recombinant Boophilus annulatus Bm86 ortholog protein, Ba86, protects cattle against B. annulatus and B. microplus infestations

Diseases caused by arthropod-borne pathogens greatly impact on human and animal health. Recent research has provided evidence that tick protective antigens can be used for development of vaccines with the dual target of controlling arthropod infestations and reducing their vector capacity for pathogens. As reviewed herein, protective antigens such as subolesin/akirin, which are highly conserved across vector species, show promise for use in development of a universal vaccine for the control of arthropod infestations and the reduction of pathogen transmission. However, further research is needed in critical areas towards achieving this goal.

Characterization of ferritin 2 for the control of tick infestations.

BackgroundThe cattle ticks, Boophilus spp., affect cattle production in tropical and subtropical regions of the world. Tick vaccines constitute a cost-effective and environmentally friendly alternative to tick control. The recombinant B. microplus Bm86 protective antigen has been shown to protect cattle against tick infestations. Recently, the gene coding for B. annulatus Bm86 ortholog, Ba86, was cloned and the recombinant protein was secreted and purified from the yeast Pichia pastoris.ResultsRecombinant Ba86 (Israel strain) was used to immunize cattle to test its efficacy for the control of B. annulatus (Mercedes, Texas, USA strain) and B. microplus (Susceptible, Mexico strain) infestations. Bm86 (Gavac and Mozambique strain) and adjuvant/saline were used as positive and negative controls, respectively. Vaccination with Ba86 reduced tick infestations (71% and 40%), weight (8% and 15%), oviposition (22% and 5%) and egg fertility (25% and 50%) for B. annulatus and B. microplus, respectively. The efficacy of both Ba86 and Bm86 was higher for B. annulatus than for B. microplus. The efficacy of Ba86 was higher for B. annulatus (83.0%) than for B. microplus (71.5%). The efficacy of Bm86 (Gavac; 85.2%) but not Bm86 (Mozambique strain; 70.4%) was higher than that of Ba86 (71.5%) on B. microplus. However, the efficacy of Bm86 (both Gavac and Mozambique strain; 99.6%) was higher than that of Ba86 (83.0%) on B. annulatus.ConclusionThese experiments showed the efficacy of recombinant Ba86 for the control of B. annulatus and B. microplus infestations in cattle and suggested that physiological differences between B. microplus and B. annulatus and those encoded in the sequence of Bm86 orthologs may be responsible for the differences in susceptibility of these tick species to Bm86 vaccines.