Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases

Neelakanta, Girish; Sultana, Hameeda

doi:10.1007/s00005-014-0324-8

Cited by 48 publications

(56 citation statements)

References 110 publications

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“…Potential future magic bullet solutions, capable of both ensuring that the bite of an infected tick does not result in illness and having the potential to rapidly and dramatically reduce I. scapularis -borne human infections at the population level, include (i) human vaccines or prophylactic antibody treatments against Lyme disease spirochetes or other I. scapularis -borne pathogens [104,105,109,110], and (ii) transmission-blocking anti-tick vaccines for human use with potential for simultaneous protection against multiple I. scapularis -borne pathogens [111–115]. These approaches would not require daily action and vigilance, and they would be effective regardless of whether or not bites by infected ticks are noticed.…”

Section: Controlling I Scapularis and Reducing Tick-borne Diseases Imentioning

confidence: 99%

The Blacklegged Tick, Ixodes scapularis : An Increasing Public Health Concern

Eisen

2018

Trends in Parasitology

282

202

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In the United States, the blacklegged tick, Ixodes scapularis, is a vector of seven human pathogens, including those causing Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate of discovery of I. scapularis-borne pathogens over the past two decades, the geographic range of the tick, and incidence and range of I. scapularis-borne disease cases, have increased. Despite knowledge of when and where humans are most at risk of exposure to infected ticks, control of I. scapularis-borne diseases remains a challenge. Human vaccines are not available, and we lack solid evidence for other prevention and control methods to reduce human disease. The way forward is discussed.

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Section: Controlling I Scapularis and Reducing Tick-borne Diseases Imentioning

confidence: 99%

The Blacklegged Tick, Ixodes scapularis : An Increasing Public Health Concern

Eisen

2018

Trends in Parasitology

282

202

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“…Besides being a critical component of the feeding process, saliva has also been shown to play a role in pathogen transmission [ 21 ]. Therefore, the identification and characterization of novel H. longicornis saliva proteins could point to candidates for the development of anti-tick and transmission-blocking vaccines [ 22 – 26 ] and of new pharmacological active molecules for medical application [ 18 , 20 , 27 – 29 ].…”

Section: Introductionmentioning

confidence: 99%

Saliva from nymph and adult females of Haemaphysalis longicornis: a proteomic study

et al. 2015

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BackgroundHaemaphysalis longicornis is a major vector of Theileria spp., Anaplasma phagocytophilum, Babesia spp. and Coxiella burnetti in East Asian countries. All life stages of ixodid ticks have a destructive pool-feeding style in which they create a pool-feeding site by lacerating host tissue and secreting a variety of biologically active compounds that allows the tick to evade host responses, enabling the uptake of a blood meal. The identification and functional characterization of tick saliva proteins can be useful to elucidate the molecular mechanisms involved in tick development and to conceive new anti-tick control methods.MethodsH. longicornis tick saliva was collected from fully engorged nymphs and fully engorged adults induced by dopamine or pilocarpine, respectively. Saliva was digested with trypsin for LC-MS/MS sequencing and peptides were searched against tick and rabbit sequences.ResultsA total of 275 proteins were identified, of which 135 were tick and 100 were rabbit proteins. Of the tick proteins, 30 proteins were identified exclusively in fully engorged nymph saliva, 74 in fully engorged adult females, and 31 were detected in both stages. The identified tick proteins include heme/iron metabolism-related proteins, oxidation/detoxification proteins, enzymes, proteinase inhibitors, tick-specific protein families, and cytoskeletal proteins. Proteins involved in signal transduction, transport and metabolism of carbohydrate, energy, nucleotide, amino acids and lipids were also detected. Of the rabbit proteins, 13 were present in nymph saliva, 48 in adult saliva, and 30 were present in both. The host proteins include immunoglobulins, complement system proteins, antimicrobial proteins, serum albumin, peroxiredoxin, serotransferrin, apolipoprotein, hemopexin, proteinase inhibitors, and hemoglobin/red blood cells-related products.ConclusionsThis study allows the identification of H. longicornis saliva proteins. In spontaneously detached tick saliva various proteins were identified, although results obtained with saliva of fully engorged ticks need to be carefully interpreted. However, it is interesting to note that proteins identified in this study were also described in other tick saliva proteomes using partially engorged tick saliva, including hemelipoprotein, proteases, protease inhibitors, proteins related to structural functions, transporter activity, metabolic processes, and others. In conclusion, these data can provide a deeper understanding to the biology of H. longicornis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-0918-y) contains supplementary material, which is available to authorized users.

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“…The roles of vector molecules and their mechanisms in transmission of arthropod-borne flaviviruses from vector to vertebrate host are not completely understood. Targeting essential vector molecules used by flaviviruses during transmission to the vertebrate host is envisioned as the best approach to develop therapeutics and vaccine candidates (3). Currently, there are no specific drugs/therapies or vaccines for several of these arthropodborne flaviviral infections (4)(5)(6).…”

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confidence: 99%

Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb

Vora

Zhou

Londoño-Rentería

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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129

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Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from and, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naïve human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb.

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Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases

Cited by 48 publications

References 110 publications

The Blacklegged Tick, Ixodes scapularis : An Increasing Public Health Concern

The Blacklegged Tick, Ixodes scapularis : An Increasing Public Health Concern

Saliva from nymph and adult females of Haemaphysalis longicornis: a proteomic study

Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb

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