Tick vaccines: current status and future directions

Fuente, José de la; Contreras, Marinela

doi:10.1586/14760584.2015.1076339

Cited by 111 publications

(126 citation statements)

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“…Despite the growing burden that A. phagocytophilum and other tick-borne pathogens represent for human and animal health worldwide, effective control measures have not been developed [59]. Investigating the biological relevance of host proteins in tick biology and pathogen infection and the mechanisms used by A. phagocytophilum to manipulate host protein content is essential to advance our knowledge of tick-host-pathogen molecular interactions.…”

Section: Discussionmentioning

confidence: 99%

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

et al. 2016

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BackgroundThe intracellular bacteria Anaplasma phagocytophilum are emerging zoonotic pathogens affecting human and animal health, and a good model for the study of tick-host-pathogen interactions. This tick-borne pathogen is transmitted by Ixodes scapularis in the United States where it causes human granulocytic anaplasmosis. Tick midguts and salivary glands play a major role during tick feeding and development, and in pathogen acquisition, multiplication and transmission. Vertebrate host proteins are found in tick midguts after feeding and have been described in the salivary glands of fed and unfed ticks, suggesting a role for these proteins during tick feeding and development. Furthermore, recent results suggested the hypothesis that pathogen infection affects tick metabolic processes to modify host protein digestion and persistence in the tick with possible implications for tick physiology and pathogen life-cycle.MethodsTo address this hypothesis, herein we used I. scapularis female ticks fed on uninfected and A. phagocytophilum-infected sheep to characterize host protein content in midguts and salivary glands by proteomic analysis of tick tissues.ResultsThe results evidenced a clear difference in the host protein content between tick midguts and salivary glands in response to infection suggesting that A. phagocytophilum selectively manipulates the levels of vertebrate host proteins in ticks in a tissue-specific manner to facilitate pathogen infection, multiplication and transmission while preserving tick feeding and development. The mechanisms by which A. phagocytophilum manipulates the levels of vertebrate host proteins are not known, but the results obtained here suggested that it might include the modification of proteolytic pathways.ConclusionsThe results of this study provided evidence to support that A. phagocytophilum affect tick proteolytic pathways to selectively manipulate the levels of vertebrate host proteins in a tissue-specific manner to increase tick vector capacity. Investigating the biological relevance of host proteins in tick biology and pathogen infection and the mechanisms used by A. phagocytophilum to manipulate host protein content is essential to advance our knowledge of tick-host-pathogen molecular interactions. These results have implications for the identification of new targets for the development of vaccines for the control of tick-borne diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1747-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

et al. 2016

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“…With respect to the tick innate immune response, A. phagocytophilum subverts tick RNAi by mechanisms other than reduction of Tudor staphylococcal nuclease (Tudor-SN) levels to preserve a protein that is important for tick feeding (Ayllón et al, 2015b). In contrast, Subolesin (SUB), also involved in tick innate immune response for limiting pathogen infection (Naranjo et al, 2013; de la Fuente and Contreras, 2015), is not manipulated by A. phagocytophilum . SUB has been shown to be required for tick feeding and reproduction and for pathogen infection, and therefore the preservation of this protein is important for both tick and pathogen survival (de la Fuente and Contreras, 2015).…”

Section: Biological Processes Involved In Tick-pathogen Interactionsmentioning

confidence: 99%

“…In contrast, Subolesin (SUB), also involved in tick innate immune response for limiting pathogen infection (Naranjo et al, 2013; de la Fuente and Contreras, 2015), is not manipulated by A. phagocytophilum . SUB has been shown to be required for tick feeding and reproduction and for pathogen infection, and therefore the preservation of this protein is important for both tick and pathogen survival (de la Fuente and Contreras, 2015). In I. scapularis , the x-linked inhibitor of apoptosis protein (XIAP) interacts with the E2 conjugating enzyme Bendless affecting positive and negative regulators of the immune deficiency (IMD) pathway resulting in protection against infection by A. phagocytophilum (Severo et al, 2013).…”

Section: Biological Processes Involved In Tick-pathogen Interactionsmentioning

confidence: 99%

“…As shown for B. burgdorferi OspA (Gomes-Solecki, 2014), pathogen-derived proteins involved in interactions with tick cells and playing a role during infection provide targets for development of novel control strategies for pathogen infection and transmission. Similarly, tick-derived antigens such as SUB involved in different biological processes may be used to reduce vector infestations and pathogen infection in ticks feeding on immunized animals (de la Fuente and Contreras, 2015). One novel approach to control populations might be to target specific endosymbionts, which requires detailed knowledge of microbial communities and their impact on tick biology (Taylor et al, 2012).…”

Section: Conclusion and Future Directions For The Control Of Tick-bomentioning

confidence: 99%

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Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

Fuente

Antunes

Bonnet

et al. 2017

Front. Cell. Infect. Microbiol.

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Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.

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“…However, this approach generates undesired consequences such as the selection of acaricide resistant tick populations and contamination of the environment and animal products [6,7]. In this scenario, alternative tick control methods, such as vaccination, are increasingly needed [8,9]. …”

Section: Introductionmentioning

confidence: 99%

Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

et al. 2016

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The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST). The B. bovis S74-T3B parasites were electroporated with a plasmid containing the bidirectional Ef-1α (elongation factor 1 alpha) promoter of B. bovis controlling expression of two independent genes, the selectable marker GFP-BSD (green fluorescent protein–blasticidin deaminase), and HlGST fused to the MSA-1 (merozoite surface antigen 1) signal peptide from B. bovis. Electroporation followed by blasticidin selection resulted in the emergence of a mixed B. bovis transfected line (termed HlGST) in in vitro cultures, containing parasites with distinct patterns of insertion of both exogenous genes, either in or outside the Ef-1α locus. A B. bovis clonal line termed HlGST-Cln expressing intracellular GFP and HlGST in the surface of merozoites was then derived from the mixed parasite line HlGST using a fluorescent activated cell sorter. Two independent calf immunization trials were performed via intravenous inoculation of the HlGST-Cln and a previously described control consisting of an irrelevant transfected clonal line of B. bovis designated GFP-Cln. The control GFP-Cln line contains a copy of the GFP-BSD gene inserted into the Ef-1α locus of B. bovis in an identical fashion as the HIGST-Cln parasites. All animals inoculated with the HlGST-Cln and GFP-Cln transfected parasites developed mild babesiosis. Tick egg fertility and fully engorged female tick weight was reduced significantly in R. microplus feeding on HlGST-Cln-immunized calves. Collectively, these data show the efficacy of a transfected HlGST-Cln B. bovis parasite to induce detectable anti-glutathione-S-transferase antibodies and a reduction in tick size and fecundity of R. microplus feeding in experimentally inoculated animals.

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Tick vaccines: current status and future directions

Cited by 111 publications

References 111 publications

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

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