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

Ndawula, Charles; Sabadin, Gabriela Alves; Parizi, Luís Fernando; Vaz, Itabajara da Silva

doi:10.1016/j.vaccine.2019.02.039

Cited by 29 publications

(34 citation statements)

References 62 publications

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“…Recently, the principle of independent immunogenicity of tick vaccine antigens has further been investigated toward selecting cocktail antigens [ 45 ]. Specifically, Ndawula et al [ 45 ] demonstrated that serum independently induced against the recombinant glutathione S-transferase (rGST) cross-reacts against heterologous tick species rGSTs, although at varying intensities. Interestingly, a similar approach was earlier used toward identifying a potential broad-spectrum single tick vaccine antigen based on tick cement [ 40 ].…”

Section: Approaches To Identifying Cocktail Vaccine Antigensmentioning

confidence: 99%

“…However, currently Freunds’ adjuvants are not recommended for commercial use in large animals, as they induce tissue damage and painful reactions following vaccination [ 94 ]. For these reasons, alternatives to Freunds’ adjuvants, the Montanide (‘oil-in-water’) adjuvants have been used in several cocktail studies summarized in Table 1 [ 38 , 45 , 74 , 95 , 96 , 97 , 98 ]. Until now, however, few studies have examined the effect of different adjuvants on cocktail vaccine efficacies [ 73 , 92 , 95 , 99 ].…”

Section: Potential Constraints Toward Cocktail Vaccine Efficacymentioning

confidence: 99%

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Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

Ndawula

Lew-Tabor

2020

Vaccines

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Ticks are second to mosquitoes as vectors of disease. Ticks affect livestock industries in Asia, Africa and Australia at ~$1.13 billion USD per annum. For instance, 80% of the global cattle population is at risk of infestation by the Rhipicephalus microplus species-complex, which in 2016 was estimated to cause $22–30 billion USD annual losses. Although the management of tick populations mainly relies on the application of acaricides, this raises concerns due to tick resistance and accumulation of chemical residues in milk, meat, and the environment. To counteract acaricide-resistant tick populations, immunological tick control is regarded among the most promising sustainable strategies. Indeed, immense efforts have been devoted toward identifying tick vaccine antigens. Until now, Bm86-based vaccines have been the most effective under field conditions, but they have shown mixed success worldwide. Currently, of the two Bm86 vaccines commercialized in the 1990s (GavacTM in Cuba and TickGARDPLUSTM in Australia), only GavacTM is available. There is thus growing consensus that combining antigens could broaden the protection range and enhance the efficacies of tick vaccines. Yet, the anticipated outcomes have not been achieved under field conditions. Therefore, this review demystifies the potential limitations and proposes ways of sustaining enhanced cocktail tick vaccine efficacy.

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Section: Approaches To Identifying Cocktail Vaccine Antigensmentioning

confidence: 99%

Section: Potential Constraints Toward Cocktail Vaccine Efficacymentioning

confidence: 99%

Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

Ndawula

Lew-Tabor

2020

Vaccines

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“…As mentioned in the literature review that a number of tick protective antigens have been found to be useful in tick control (de la Fuente 2018). The tick GSTs were also investigated as potential candidates for vaccination against many tick species, and reached a protective effect by reducing repletion rate and egg production of female adult ticks, and egg hatchability (Huercha et al 2020;Ndawula et al 2019;Oldiges et al 2016;Sabadin et al 2017). The GSTs are a superfamily present in eukaryotes and prokaryotes that are generally involved in the detoxification of endogenous and xenobiotic compounds (Ketterman et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the conformation epitope prediction results indicated that mu-class GST may generate stronger B-cell immune response than other three classes of GSTs in this study. A previous study of a GST-cocktail vaccine against five species of ticks has obtained 35% efficacy, suggesting that the mu-class GST is a potential target of broad-spectrum antigens against ticks (Ndawula et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Sequence identification and expression profile of seven Dermacentor marginatus glutathione S-transferase genes

Huercha

Hao

et al. 2020

Exp Appl Acarol

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Dermacentor marginatus is a widespread tick species and a vector of many pathogens in Eurasia. Due to the medical importance of D. marginatus, control measures are needed for this tick species. Currently tick control approaches rely mostly on acaricide application, whereas wrong and irrational acaricide use may result in drug resistance and residue problems. Vaccination as an alternative approach for tick control has been proven to be effective towards some tick species. However, immunization against D. marginatus has not yet reached satisfactory protection. The effort of in silico based analysis could predict antigenicity and identify candidates for anti-tick vaccine development. We carried out an in silico analysis of D. marginatus glutathione S-transferases (DmGSTs) in order to identify blood-feeding induced GSTs as antigens that can be used in anti-tick vaccine development. Phylogenetic analysis, linear B-cell epitope prediction, homology modeling, and conformational B-cell epitope mapping on the GST models were performed to identify highly antigenic DmGSTs. Relative gene expressions of the seven GSTs were profiled through real-time quantitative PCR (RT-qPCR) to outline GSTs up-regulated during blood feeding. The phylogenetic analysis indicated that the seven GSTs belonged to four classes of GST, including one in epsilon-class, one in zeta-class, one in omega-class, and four in mu-class. Linear B-cell epitope prediction revealed mu-class GSTs share similar conserved antigenic regions. The conformational B-cell epitope mapped on the homology model of the GSTs displayed that GSTs of mu-class showed stronger antigenicity than that of other classes. RT-qPCR revealed DmGSTM1 and DmGSTM2 were positively related to blood feeding. In sum, the data suggest that DmGSTM1 and DmGSTM2 could be tested for potential antitick vaccine trials.

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“…In A. aegypti, GST transcription increases only after blood feeding, which does not occur after sugar feeding [7]. Moreover, GST was used as a protective vaccine antigen against ticks in diverse works [55,64,65,73], showing its potential to compose an efficient vaccine. In R. prolixus, it was described an intense production of H 2 O 2 and increased expression of superoxide dismutase and catalase enzymes after blood feeding [62].…”

Section: Hematophagousmentioning

confidence: 99%

Control of Redox Homeostasis in Tick Blood Feeding

Sabadin¹,

Xavier²,

Vaz³

2019

Acta Scientiae. Vet.

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Introduction:Ticks are hematophagous ectoparasites that cause significate economical losses. Acaricide application is the main method to tick control. However, it causes environmental contamination and selects resistant ticks. The immunological control represents a suitable method to replace or complement acaricide application. During its life cycle, female ticks ingest large amounts of blood, which contains toxic components able to damage biomolecules. Understanding which molecular mechanisms and proteins are involved in avoid damages caused by blood intake in ticks and other hematophagous arthropods could help to found potential candidate antigens to compose an anti-tick vaccine. Review: Hemoglobin comprises almost 20% of mammalian blood proteins, its hydrolysis during tick digestion increases total free heme that can potentially generate reactive oxygen species (ROS), which easily oxidize lipids, proteins and DNA, modifying they structure and function. Lipids are more susceptible to high ROS levels. It can lead to membrane instability and cell death. Protein modifications caused by ROS can promote the protein loss of function and cell disturbance, however, it can also work as post-translational modifications, acting in cell signaling processes. DNA presents more efficient protective mechanisms against ROS, but damages can lead to double helix rupture. Oxidative stress is defined as a disturbance in the balance between the production and elimination of ROS, in favor of ROS production, leading to a disruption in redox homeostasis and/or molecular damage. Despite the well-recognized heme oxidative power and its already demonstrated cytotoxicity, ticks are able to feed on blood, controlling the redox homeostasis without causing oxidative stress. This occurs because ticks developed physiological adaptations to transport, store, metabolize and secrete toxic components from the diet. The strategies, such as heme compartmentalization in specialized organelles, and heme and iron carrying proteins are shared with most of other hematophagous. Interesting, heme degradation, a mechanism commonly described in hematophagous arthropods, showed to be absent in ticks. Moreover, there is a lack of key enzymes from the heme degradation pathway in tick genomes. As expected, antioxidant enzymes are often involved in homeostasis redox control. They act in a convenient way, eliminating physiological and non-physiological produced ROS. Despite their essential role in nonhematophagous organisms, antioxidant enzymes were associated with blood ingestion during arthropod hematophagous process, demonstrating their role in avoiding oxidative stress caused by blood intake. Catalase showed to be essential to heme detoxification in Rhipicephalus microplus tick, and diverse antioxidant enzymes are up-regulated after blood intake in a variety of hematophagous parasites. If in one hand ROS is responsible to cell damage and oxidative stress, on the other hand, several works revealed the fundamental role of ROS in cell signaling and function, demon...

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

Cited by 29 publications

References 62 publications

Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

Sequence identification and expression profile of seven Dermacentor marginatus glutathione S-transferase genes

Control of Redox Homeostasis in Tick Blood Feeding

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