Lesser protein degradation machinery correlates with higher BM86 tick vaccine efficacy in Rhipicephalus annulatus when compared to Rhipicephalus microplus

Infestations with cattle ticks, Rhipicephalus (Boophilus) microplus and Rhipicephalus annulatus, economically impact cattle production in tropical and subtropical regions of the world. Vaccines containing the recombinant R. microplus BM86 gut antigen were developed and commercialized to induce an immunological protection in cattle against tick infestations. These vaccines demonstrated that tick control by vaccination is cost-effective, reduces environmental contamination and prevents the selection of drug resistant ticks that result from repeated acaricide applications. The protection elicited by BM86-containing vaccines against tick infestations is mediated by a collaborative action between the complement system and IgG antibodies. The efficacy of the vaccination with BM86 and other tick antigens is always higher for R. annulatus than against R. microplus, suggesting that tick genetic and/or physiological factors may affect tick vaccine efficacy. These factors may be related to BM86 protein levels or tick physiological processes such as feeding and protein degradation that could result in more efficient antibody–antigen interactions and vaccine efficacy. To test this hypothesis, we compared the proteome in R. annulatus and R. microplus female ticks after feeding on BM86-vaccinated and control cattle. The results showed that cattle proteins were under represented in R. annulatus when compared to R. microplus, suggesting that R. annulatus ticks ingested less blood, a difference that increased when feeding on vaccinated cattle, probably reflecting the effect of antibody–BM86 interactions on this process. The results also showed that tick protein degradation machinery was under represented in R. annulatus when compared to R. microplus. BM86 mRNA and protein levels were similar in both tick species, suggesting that lesser protease activity in R. annulatus results in more efficient antibody–antigen interactions and higher vaccine efficacy. These results have important implications for tick vaccine research, indicating that not only genetic differences, but also physiological factors may influence tick vaccine efficacy.     

Vaccination with proteins involved in tick–pathogen interactions reduces vector infestations and pathogen infection

Tick-borne pathogens cause diseases that greatly impact animal health and production worldwide. The ultimate goal of tick vaccines is to protect against tick-borne diseases through the control of vector infestations and reducing pathogen infection and transmission. Tick genetic traits are involved in vector–pathogen interactions and some of these molecules such as Subolesin (SUB) have been shown to protect against vector infestations and pathogen infection. Based on these premises, herein we characterized the efficacy of cattle vaccination with tick proteins involved in vector–pathogen interactions, TROSPA, SILK, and Q38 for the control of cattle tick, Rhipicephalus (Boophilus) microplus infestations and infection with Anaplasma marginale and Babesia bigemina. SUB and adjuvant/saline placebo were used as positive and negative controls, respectively. The results showed that vaccination with Q38, SILK and SUB reduced tick infestations and oviposition with vaccine efficacies of 75% (Q38), 62% (SILK) and 60% (SUB) with respect to ticks fed on placebo control cattle. Vaccination with TROSPA did not have a significant effect on any of the tick parameters analyzed. The results also showed that vaccination with Q38, TROSPA and SUB reduced B. bigemina DNA levels in ticks while vaccination with SILK and SUB resulted in lower A. marginale DNA levels when compared to ticks fed on placebo control cattle. The positive correlation between antigen-specific antibody titers and reduction of tick infestations and pathogen infection strongly suggested that the effect of the vaccine was the result of the antibody response in vaccinated cattle. Vaccination and co-infection with A. marginale and B. bigemina also affected the expression of genes encoding for vaccine antigens in ticks fed on cattle. These results showed that vaccines using tick proteins involved in vector–pathogen interactions could be used for the dual control of tick infestations and pathogen infection.     

Vaccination with BM86, subolesin and akirin protective antigens for the control of tick infestations in white tailed deer and red deer

Red deer (Cervus elaphus) and white-tailed deer (Odocoileus virginianus) are hosts for different tick species and tick-borne pathogens and play a role in tick dispersal and maintenance in some regions. These factors stress the importance of controlling tick infestations in deer and several methods such as culling and acaricide treatment have been used. Tick vaccines are a cost-effective alternative for tick control that reduced cattle tick infestations and tick-borne pathogens prevalence while reducing the use of acaricides. Our hypothesis is that vaccination with vector protective antigens can be used for the control of tick infestations in deer. Herein, three experiments were conducted to characterize (1) the antibody response in red deer immunized with recombinant BM86, the antigen included in commercial tick vaccines, (2) the antibody response and control of cattle tick infestations in white-tailed deer immunized with recombinant BM86 or tick subolesin (SUB) and experimentally infested with Rhipicephalus (Boophilus) microplus, and (3) the antibody response and control of Hyalomma spp. and Rhipicephalus spp. field tick infestations in red deer immunized with mosquito akirin (AKR), the SUB ortholog and candidate protective antigen against different tick species and other ectoparasites. The results showed that deer produced an antibody response that correlated with the reduction in tick infestations and was similar to other hosts vaccinated previously with these antigens. The overall vaccine efficacy was similar between BM86 (E = 76%) and SUB (E = 83%) for the control of R. microplus infestations in white-tailed deer. The field trial in red deer showed a 25-33% (18-40% when only infested deer were considered) reduction in tick infestations, 14-20 weeks after the first immunization. These results demonstrated that vaccination with vector protective antigens could be used as an alternative method for the control of tick infestations in deer to reduce tick populations and dispersal in regions where deer are relevant hosts for these ectoparasites.     

Identification of protective antigens by RNA interference for control of the lone star tick, Amblyomma americanum

The lone star tick, Amblyomma americanum, vectors pathogens of emerging diseases of humans and animals in the United States. Currently, measures are not available for effective control of A. americanum infestations. Development of vaccines directed against tick proteins may reduce tick infestations and the transmission of tick-borne pathogens. However, the limiting step in tick vaccine development has been the identification of tick protective antigens. Herein, we report the application of RNA interference (RNAi) for screening an A. americanum cDNA library for discovery of tick protective antigens that reduce tick survival and weights after feeding. Four cDNA clones, encoding for putative threonyl-tRNA synthetase (2C9), 60S ribosomal proteins L13a (2D10) and L13e (2B7), and interphase cytoplasm foci protein 45 (2G7), were selected for vaccine studies in cattle, along with subolesin, a tick protective protein identified previously. In vaccinated cattle, an overall efficacy (E) > 30% was obtained when considering the vaccine effect on both nymphs and adults, but only 2D10, 2G7 and subolesin affected both tick stages. The highest efficacy of control for adult ticks (E > 55%) was obtained in cattle vaccinated with recombinant 2G7 or subolesin. These collective results demonstrated the feasibility of developing vaccines for the control of lone star tick infestations. The use of RNAi for identification of tick protective antigens proved to be a rapid and cost-effective tool for discovery of candidate vaccine antigens, and this approach could likely be applied to other parasites of veterinary and medical importance.     

Protective efficacy of bacterial membranes containing surface-exposed BM95 antigenic peptides for the control of cattle tick infestations

The Rhipicephalus (Boophilus) microplus BM86 and BM95 glycoproteins are homologous proteins that protect cattle against tick infestations. In this study, we demonstrated that the recombinant chimeric protein comprising tick BM95 immunogenic peptides fused to the A. marginale MSP1a N-terminal region for presentation on the Escherichia coli membrane was protective against R. microplus infestations in rabbits. This system provides a novel and simple approach for the production of tick protective antigens by surface display of antigenic protein chimera on live E. coli and suggests the possibility of using recombinant bacterial membrane fractions for vaccination against cattle tick infestations.     

Efficacy of Hyalomma scupense (Hd86) antigen against Hyalomma excavatum and H. scupense tick infestations in cattle

The Rhipicephalus microplus recombinant Bm86-based tick vaccines have shown their efficacy for the control of several Hyalomma cattle ticks genera, namely H. dromedarii and H. anatolicum. However, H. scupense species, the most important tick in North Africa has never been studied. Vaccination trials using either a recombinant Bm86-based vaccine or a recombinant Hd86-based vaccine (the Bm86 ortholog in H. scupense) were conducted in cattle against immature and adult H. scupense ticks and adult H. excavatum ticks. The results showed a 59.19% reduction in the number of scupense nymphs engorging on Hd86 vaccinated cattle. However, cattle vaccination with Bm86 or Hd86 did not have an effect on H. scupense or H. excavatum adult ticks infestations. These results showed that Hd86 vaccines are selectively effective against H. scupense immature instars and emphasize on an integrated anti-tick vaccine control in North Africa.     

Constituting a glutathione S-transferase-cocktail vaccine against tick infestation

Cocktail vaccines are proposed as an attractive way to increase protection efficacy against specific tick species. Furthermore, such vaccines made with different tick antigens have the potential of cross-protecting against a broad range of tick species. However, there are still limitations to the selection of immunogen candidates. Acknowledging that glutathione S-transferases (GSTs) have been exploited as vaccines against ticks and other parasites, this study aimed to analyze a GST-cocktail vaccine as a potential broad-spectrum tick vaccine. To constitute the GST-cocktail vaccine, five tick species of economic importance for livestock industry were studied (Rhipicephalus appendiculatus, Rhipicephalus decoloratus, Rhipicephalus microplus, Amblyomma variegatum, and Haemaphysalis longicornis). Tick GST ORF sequences were cloned, and the recombinant GSTs were produced in Escherichia coli. rGSTs were purified and inoculated into rabbits, and the immunological response was characterized. The humoral response against rGST-Rd and rGST-Av showed a stronger cross-reactivity against heterologous rGSTs compared to rGST-Hl, rGST-Ra, and rGST-Rm. Therefore, rGST-Rd and rGST-Av were selected for constituting an experimental rGST-cocktail vaccine. Vaccination experiment in rabbits showed that rGST-cocktail caused 35% reduction in female numbers in a Rhipicephalus sanguineus infestation. This study brings forward an approach to selecting immunogens for cocktail vaccines, and the results highlight rGST–Rd and rGST-Av as potentially useful tools for the development of a broad-spectrum tick vaccine.     

Control of tick infestations in cattle vaccinated with bacterial membranes containing surface-exposed tick protective antigens

Vaccines containing the Rhipicephalus (Boophilus) microplus BM86 and BM95 antigens protect cattle against tick infestations. Tick subolesin (SUB), elongation factor 1a (EF1a) and ubiquitin (UBQ) are new candidate protective antigens for the control of cattle tick infestations. Previous studies showed that R. microplus BM95 immunogenic peptides fused to the Anaplasma marginale major surface protein (MSP) 1a N-terminal region (BM95-MSP1a) for presentation on the Escherichia coli membrane were protective against R. microplus infestations in rabbits. In this study, we extended these results by expressing SUB-MSP1a, EF1a-MSP1a and UBQ-MSP1a fusion proteins on the E. coli membrane using this system and demonstrating that bacterial membranes containing the chimeric proteins BM95-MSP1a and SUB-MSP1a were protective (>60% vaccine efficacy) against experimental R. microplus and Rhipicephalus annulatus infestations in cattle. This system provides a novel, simple and cost-effective approach for the production of tick protective antigens by surface display of antigenic protein chimera on the E. coli membrane and demonstrates the possibility of using recombinant bacterial membrane fractions in vaccine preparations to protect cattle against tick infestations.     

Vaccine efficacy of recombinant BmVDAC on Rhipicephalus microplus fed on Babesia bigemina-infected and uninfected cattle

Rhipicephalus microplus is the most widely distributed tick worldwide and causes significant economic losses in the livestock industry. It directly affects hosts (especially in large infestations) by feeding on blood and piercing the skin and indirectly affects hosts as a vector of pathogens that cause infectious diseases, such as bovine babesiosis. Current research on the control of ticks is focused on integrated tick control programmes, including vaccination treatment with acaricides and completely blocking pathogen transmission. Our previous studies showed that R. microplus VDAC (BmVDAC) expression is modulated by Babesia bigemina infection. VDAC is a mitochondrial protein with multiple functions in addition to its primary role as a central component of the apoptotic machinery. In this paper, we evaluated BmVDAC as an anti-tick vaccine and its capacity to block the infection of Babesia bigemina in ticks. Our results demonstrate that rBmVDAC is immunogenic and that antibodies specifically recognize the native protein from midguts of R. microplus. Immunization with rBmVDAC afforded an 82% efficacy against R. microplus infestation in the group of vaccinated cattle compared with the control group. In contrast, rBmVDAC showed a lower efficacy of 34% against tick infestation in cattle vaccinated with rBmVDAC, infested with R. microplus and infected with B. bigemina. The main effect on ticks fed in vaccinated and infected cattle was a 34% reduction in egg fertility (DF) compared to ticks fed on the control group. There was no reduction in the B. bigemina parasite levels of ticks fed on rBmVDAC-vaccinated cattle. These results suggest that the rBmVDAC protein could be tested as a vaccine for the control of tick infestation.     

Multi-antigenic vaccine against the cattle tick Rhipicephalus (Boophilus) microplus: A field evaluation

The tick Rhipicephalus (Boophilus) microplus is a blood-sucking ectoparasite of cattle that severely impairs livestock production. Studies on tick immunological control address mostly single-antigen vaccines. However, from the commercial standpoint, so far no single-antigen vaccine has afforded appropriate protection against all R. microplus populations. In this context, multi-antigen cocktails have emerged as a way to enhance vaccine efficacy. In this work, a multi-antigenic vaccine against R. microplus was analyzed under field conditions in naturally infested cattle. The vaccine was composed by three tick recombinant proteins from two tick species that in previous single-vaccination reports provided partial protection of confined cattle against R. microplus infestations: vitellin-degrading cysteine endopeptidase (VTDCE) and boophilus yolk pro-cathepsin (BYC) from R. microplus, and glutathione S-transferase from Haemaphysalis longicornis (GST-Hl). Increased antibody levels against three proteins were recorded after immunizations, with a distinct humoral immune response dynamics for each protein. Compared to the control group, a statistically significant lower number of semi-engorged female ticks were observed in vaccinated cattle after two inoculations. This reduction persisted for 3 months, ranging from 35.3 to 61.6%. Furthermore, cattle body weight gain was significantly higher in vaccinated animals when compared to control cattle. Compared to the single-antigen vaccines composed by VTDCE, BYC or GST-Hl, this three-antigen vaccine afforded higher protection levels against R. microplus infestations.     

Targeting the tick protective antigen subolesin reduces vector infestations and pathogen infection by Anaplasma marginale and Babesia bigemina

The ultimate goal of vector vaccines is the control of vector infestations while reducing pathogen infection and transmission to protect against the many diseases caused by vector-borne pathogens. Previously (Vaccine 2011;29:2248-2254), we demonstrated that subolesin vaccination and release of tick larvae after subolesin knockdown by RNA interference (RNAi) were effective for the control of cattle tick, Rhipicephalus (Boophilus) microplus infestations in cattle. In this study, we used the fact that these animals were naturally infected with Anaplasma marginale and Babesia bigemina to evaluate the effect of subolesin vaccination and gene knockdown on tick infection by these cattle tick-transmitted pathogens. Ticks fed on vaccinated cattle had lower subolesin mRNA levels when compared to controls, resembling RNAi results. A. marginale and B. bigemina infection was determined by PCR and decreased by 98% and 99%, respectively in ticks fed on vaccinated cattle and by 97% and 99%, respectively after subolesin knockdown. These results demonstrated that targeting subolesin expression by vaccination or RNAi results in lower subolesin mRNA and pathogen infection levels, probably due to the effect of subolesin downregulation on tick feeding, gene expression and gut and salivary glands tissue development and function. These results suggested that subolesin vaccines could be used for the dual control of tick infestations and pathogen infection, a result that could be relevant for other vectors and vector-borne pathogens.     

Control of Rhipicephalus (Boophilus) microplus infestations by the combination of subolesin vaccination and tick autocidal control after subolesin gene knockdown in ticks fed on cattle

Tick subolesin was shown in immunization trials using the recombinant protein to protect hosts against tick infestations. In this study, we demonstrated that subolesin vaccination and release of ticks after subolesin knockdown by RNA interference (RNAi) could be used for the control of Rhipicephalus (Boophilus) microplus tick infestations in cattle and suggested that the combination of these methods could increase the efficacy of cattle tick control under some circumstances. The greatest tick control was obtained when both release of ticks after subolesin knockdown and vaccination were used concurrently. However, modeling results suggested that vaccine efficacy could be increased if at least 80% of the ticks infesting cattle correspond to subolesin-knockdown ticks. The results of this proof-of-concept trial demonstrated the efficacy of the sterile acarine technique (SAT) through production of subolesin-knockdown larvae by dsRNA injection into replete females for the control of R. microplus tick infestations, alone or in combination with subolesin vaccination.     

Efficacy of Rhipicephalus (Boophilus) microplus Bm86 against Hyalomma dromedarii and Amblyomma cajennense tick infestations in camels and cattle

The recombinant Bm86-based tick vaccines have shown their efficacy for the control of cattle ticks, Rhipicephalus (Boophilus) microplus and R. annulatus infestations. However, cattle ticks often co-exist with multi-host ticks such as Hyalomma and Amblyomma species, thus requiring the control of multiple tick infestations for cattle and other hosts. Vaccination trials using a R. microplus recombinant Bm86-based vaccine were conducted in cattle and camels against Hyalomma dromedarii and in cattle against Amblyomma cajennense immature and adult ticks. The results showed an 89% reduction in the number of H. dromedarii nymphs engorging on vaccinated cattle, and a further 32% reduction in the weight of the surviving adult ticks. In vaccinated camels, a reduction of 27% and 31% of tick engorgement and egg mass weight, respectively was shown, while egg hatching was reduced by 39%. However, cattle vaccination with Bm86 did not have an effect on A. cajennense tick infestations. These results showed that Bm86 vaccines are effective against R. microplus and other tick species but improved vaccines containing new antigens are required to control multiple tick infestations.     

Experimental vaccination in rabbits using the peptide RmS-17 antigen reduces the performance of a Mexican Rhipicephalus microplus tick strain

The tick vector Rhipicephalus microplus is considered one of the main problems in cattle production in tropical and subtropical regions. Anti-tick vaccines may form an alternative tick control method to the use of acaricides, and tick salivary proteins, such as Serpins, may be valuable as target antigens for developing anti-tick vaccines. In this study, we synthesized a recombinant peptide derived from Serpin RmS-17 protein using an Escherichia coli expression system and characterized the efficacy of the peptide RmS-17 for the control of R. microplus females infesting rabbits. Twelve New Zealand white rabbits were assigned to three experimental groups and vaccinated with three subcutaneous doses of the peptide RmS-17, recombinant R. microplus Bm86 antigen, and adjuvant/saline alone. The tick challenge was conducted with 120 R. microplus adults (60 females and 60 males) per animal, with the ticks placed inside a cotton sleeve glued to the back of the rabbit. Serum antibody levels (IgG) were assessed by ELISA and confirmed by Western blot; also, the reproductive performance of R. microplus was determined. The results showed that experimental vaccination in rabbits using the peptide RmS-17 antigen had a vaccine efficacy of 79% based on reductions in adult tick number, oviposition, and egg fertility compared to control animals. The peptide RmS-17 vaccinated rabbits developed a strong humoral immune response expressed by high anti-pRmS-17 IgG levels, and the Western blot analysis confirmed that it is immunogenic. The efficacy for the Bm86 vaccine was 62%, which is within the range of efficacy reported previously for Bm86 vaccine. The negative correlation between antibody levels and reduction in tick number strongly suggests that the effect of the vaccine was the result of the antibody response in vaccinated rabbits. In conclusion, this is the first study to evaluate the efficacy of the peptide RmS-17 against R. microplus tick infestation and show it to be immunogenic and protective in a rabbit model.     

Control of tick infestations in wild roe deer (Capreolus capreolus) vaccinated with the Q38 Subolesin/Akirin chimera

Ticks (Acari: Ixodidae) are considered to be the most important vectors of disease-causing pathogens in domestic and wild animals, and emerging and re-emerging tick-borne diseases (TBD) exert an enormous impact on them. Wild ungulates are hosts for a wide variety of tick species and tick-borne pathogens that affect human and animal health. Consequently, the control of tick infestations and tick-borne pathogen prevalence is essential in some regions. Acaricides and animal management or culling have been used for the control of tick infestations and TBD, but tick vaccines constitute the best alternative to reduce the impact of acaricides on tick resistance and the environment. Previous results of controlled vaccination trials have shown that the Q38 Subolesin/Akirin chimera containing conserved protective epitopes could be a candidate universal antigen to control multiple tick species infestations. Thus, vaccination trials are necessary to validate these results under field conditions. In this study, we characterized the effect of Q38 vaccine on a wild population of European roe deer (Capreolus capreolus) in the Andalusian roe deer Reference Station (Junta de Andalucía, Cádiz, Spain). In this location, roe deer suffer especially severe parasitic conditions in some periods and commercial pesticides and ixodicides that are authorized to control ticks without specificity are frequently applied in the field, posing a threat to the environment. Animals vaccinated over a three-year period showed an antibody response to the vaccine antigen and a reduction in tick infestations by multiple species including Hyalomma marginatum, H. lusitanicum, Rhipicephalus bursa and Ixodes ricinus previously identified in roe deer, when compared to untreated controls. These results suggest the efficacy of Q38 for the control of tick infestations in wildlife.     

Oral vaccine formulation combining tick Subolesin with heat inactivated mycobacteria provides control of cross-species cattle tick infestations

Tick vaccines are necessary as part of a One Health approach for the control of tick infestations and tick-borne diseases. Subolesin (SUB, also known as 4D8) is a tick protective antigen that has shown efficacy in vaccine formulations for the control of ectoparasite infestations and pathogen infection/transmission. A recent proof-of-concept study reported oral vaccination combining Rhipicephalus microplus SUB with heat inactivated Mycobacterium bovis (IV) as an immunostimulant for the control of cattle tick infestations. Based on the efficacy of Rhipicephalus decoloratus SUB for the control of multiple cattle tick species in Uganda, herein we design a controlled pen trial using an oral formulation combining R. decoloratus SUB with IV for the control of R. decoloratus and Rhipicephalus appendiculatus cattle tick infestations. Vaccine efficacy (E) of SUB + IV on tick life cycle was compared with IV and SUB alone and with PBS as control. The IgG antibody titers against SUB and M. bovis P22 and the serum levels of selected protein immune biomarkers (IL-1beta, TNF-alpha, C3) were determined and analyzed as possible correlates of protection. Oral immunization with IV and SUB alone and in SUB + IV combination were effective for the control of tick infestations (E = 71–96% for R. decoloratus and 87–99% for R. appendiculatus) with highest E (higher than 95%) for SUB + IV. The results demonstrated that oral immunization with the SUB + IV formulation resulted in effective control of cattle tick infestations through the activation of multiple immune mechanisms. These results support the application of oral vaccine formulations with SUB + IV for the control of cattle infestations with Rhipicephalus species towards improving animal health.     

Control of infestations by Ixodes ricinus tick larvae in rabbits vaccinated with aquaporin recombinant antigens

BackgroundTick-borne diseases greatly impact human and animal health worldwide, and vaccines are an environmentally friendly alternative to acaricides for their control. Recent results have suggested that aquaporin (AQP) water channels have a key function during tick feeding and development, and constitute good candidate antigens for the control of tick infestations.MethodsHere we describe the effect of vaccination with the Ixodes ricinus AQP1 (IrAQP) and a tick AQP conserved region (CoAQP) on I. ricinus tick larval mortality, feeding and molting.ResultsWe demonstrated that vaccination with IrAQP and CoAQP had an efficacy of 32% and 80%, respectively on the control of I. ricinus larvae by considering the cumulative effect on reducing tick survival and molting.ConclusionsThe effect of the AQP vaccines on larval survival and molting is essential to reduce tick infestations, and extended previous results on the effect of R. microplus AQP1 on the control of cattle tick infestations. These results supports that AQP, and particularly CoAQP, might be a candidate protective antigen for the control of different tick species.     

Identification and functional analysis of ferritin 2 from the Taiga tick Ixodes persulcatus Schulze

Ferritin 2 (FER2) is an iron storage protein, which has been shown to be critical for iron homeostasis during blood feeding and reproduction in ticks and is therefore suitable as a component for anti-tick vaccines. In this study, we identified the FER2 of Ixodes persulcatus, a major vector for zoonotic diseases such as Lyme borreliosis and tick-borne relapsing fever in Japan, and investigated its functions. Ixodes persulcatus-derived ferritin 2 (Ip-FER2) showed concentration-dependent iron-binding ability and high amino acid conservation, consistent with FER2s of other tick species. Vaccines containing the recombinant Ip-FER2 elicited a significant reduction of the engorgement weight of adult I. persulcatus. Interestingly, the reduction of engorgement weight was also observed in Ixodes ovatus, a sympatric species of I. persulcatus. In silico analyses of FER2 sequences of I. persulcatus and other ticks showed a greater similarity with I. scapularis and I. ricinus and lesser similarity with Hyalomma anatolicum, Haemaphysalis longicornis, Rhipicephalus microplus, and R. appendiculatus. Moreover, it was observed that the tick FER2 sequences possess conserved regions within the primary structures, and in silico epitope mapping analysis revealed that antigenic regions were also conserved, particularly among Ixodes spp ticks. In conclusion, the data support further protective tick vaccination applications using the Ip-FER2 antigens identified herein.     

Innovative approaches for the control of ticks and tick-borne diseases

Ticks and tick-borne diseases constitute a major threat for human and animal health worldwide. Vaccines for the control of tick infestations and transmitted pathogens still represents a challenge for science and health. Vaccines have evolved with antigens derived from inactivated pathogens to recombinant proteins and vaccinomics approaches. Recently, vaccines for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown the efficacy of new antigen delivery platforms. However, until now only two vaccines based on recombinant Bm86/Bm95 antigens have been registered and commercialized for the control of cattle-tick infestations. Nevertheless, recently new technologies and approaches are under consideration for vaccine development for the control of ticks and tick-borne pathogens. Genetic manipulation of tick commensal bacteria converted enemies into friends. Frankenbacteriosis was used to control tick pathogen infection. Based on these results, the way forward is to develop new paratransgenic interventions and vaccine delivery platforms for the control of tick-borne diseases.