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

Tick-borne diseases are a potential threat that account for significant morbidity and mortality in human population worldwide. Vaccines are not available to treat several of the tick-borne diseases. With the emergence and resurgence of several tick-borne diseases, emphasis on the development of transmission-blocking vaccines remains increasing. In this review, we provide a snap shot on some of the potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against wide range of hard and soft ticks that include Ixodes, Haemaphysalis, Dermacentor, Amblyomma, Rhipicephalus and Ornithodoros species

Dermacentor reticulatus: a vector on the rise

Dermacentor reticulatus is a hard tick species with extraordinary biological features. It has a high reproduction rate, a rapid developmental cycle, and is also able to overcome years of unfavourable conditions. Dermacentor reticulatus can survive under water for several months and is cold-hardy even compared to other tick species. It has a wide host range: over 60 different wild and domesticated hosts are known for the three active developmental stages. Its high adaptiveness gives an edge to this tick species as shown by new data on the emergence and establishment of D. reticulatus populations throughout Europe. The tick has been the research focus of a growing number of scientists, physicians and veterinarians. Within the Web of Science database, more than a fifth of the over 700 items published on this species between 1897 and 2015 appeared in the last three years (2013–2015). Here we attempt to synthesize current knowledge on the systematics, ecology, geographical distribution and recent spread of the species and to highlight the great spectrum of possible veterinary and public health threats it poses. Canine babesiosis caused by Babesia canis is a severe leading canine vector-borne disease in many endemic areas. Although less frequently than Ixodes ricinus, D. reticulatus adults bite humans and transmit several Rickettsia spp., Omsk haemorrhagic fever virus or Tick-borne encephalitis virus. We have not solely collected and reviewed the latest and fundamental scientific papers available in primary databases but also widened our scope to books, theses, conference papers and specialists colleagues’ experience where needed. Besides the dominant literature available in English, we also tried to access scientific literature in German, Russian and eastern European languages as well. We hope to inspire future research projects that are necessary to understand the basic life-cycle and ecology of this vector in order to understand and prevent disease threats. We conclude that although great strides have been made in our knowledge of the eco-epidemiology of this species, several gaps still need to be filled with basic research, targeting possible reservoir and vector roles and the key factors resulting in the observed geographical spread of D. reticulatus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1599-x) contains supplementary material, which is available to authorized users

Nucleic acid-based infectious and pseudoinfectious flavivirus vaccines

The genus Flavivirus contains a number of important pathogens of humans including yellow fever virus (YFV), dengue virus (DENV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and West Nile virus (WNV). Despite causing significant morbidity and mortality worldwide, commercially available vaccines only exist for YFV (live-attenuated), TBEV, and JEV (inactivated). Flavivirus vaccine research has been driven by the need for cheap, safe, thermally stable, and efficacious preparations amenable to use in developing nations. The creation of infectious cDNA clones of various flaviviruses has led to the development of genetically engineered, nucleic acid-delivered, attenuated live vaccine candidates. These provide effective immunity from a single immunisation, however share the same safety concerns as traditional live-attenuated vaccines. The generation of large internal deletions in the capsid gene of flavivirus genomes create; a vaccine that secretes large amounts of immunogenic prM/E particles from;elf-replicating RNA but does not form a spreading infection. Packaging of these capsid-deleted RNAs into virus-like particles (VLPs) using a cell line that produces capsid gene from another expression vector creates a pseudo-infectious vaccine that elicits a highly efficient immune response from a single dose and is safer than infectious virus. However, production of these VLPs is cumbersome and the resulting product is heat labile. Providing the capsid gene in trans from another promoter but within the same plasmid DNA as the capsid-deleted viral genome creates a DNA vaccine capable of producing VLPs in vivo. Uptake of this plasmid DNA results in the generation of self-replicating, capsid-deleted RNA and the capsid protein in the same cell, leading to production of secreted single-round infectious particles (SRIPs). These SRIPs then deliver capsid-deleted RNA to adjacent cells where it replicates to produce more prM/E particles. As functional capsid cannot be produced in SRIP-infected cells, further spread does not occur. SRIP-producing DNA was shown to be highly effective in mice and horses and provides an easier to manufacture and thermally stable alternative to other vaccine candidates currently being developed