Immunomic Investigation of Holocyclotoxins to Produce the First Protective Anti-Venom Vaccine Against the Australian Paralysis Tick, Ixodes holocyclus

Venom producing animals are ubiquitously disseminated among vertebrates and invertebrates such as fish, snakes, scorpions, spiders, and ticks. Of the ~890 tick species worldwide, 27 have been confirmed to cause paralysis in mammalian hosts. The Australian paralysis tick (Ixodes holocyclus) is the most potent paralyzing tick species known. It is an indigenous three host tick species that secretes potent neurotoxins known as holocyclotoxins (HTs). Holocyclotoxins cause a severe and harmful toxicosis leading to a rapid flaccid paralysis which can result in death of susceptible hosts such as dogs. Antivenins are generally polyclonal antibody treatments developed in sheep, horses or camels to administer following bites from venomous creatures. Currently, the methods to prevent or treat tick paralysis relies upon chemical acaricide preventative treatments or prompt removal of all ticks attached to the host followed by the administration of a commercial tick-antiserum (TAS) respectively. However, these methods have several drawbacks such as poor efficacies, non-standardized dosages, adverse effects and are expensive to administer. Recently the I. holocyclus tick transcriptome from salivary glands and viscera reported a large family of 19 holocyclotoxins at 38-99% peptide sequence identities. A pilot trial demonstrated that correct folding of holocyclotoxins is needed to induce protection from paralysis. The immunogenicity of the holocyclotoxins were measured using commercial tick antiserum selecting HT2, HT4, HT8 and HT11 for inclusion into the novel cocktail vaccine. A further 4 HTs (HT1, HT12, HT14 and HT17) were added to the cocktail vaccine to ensure that the sequence variation among the HT protein family was encompassed in the formulation. A second trial comparing the cocktail of 8 HTs to a placebo group demonstrated complete protection from tick challenge. Here we report the first successful anti-venom vaccine protecting dogs from tick paralysis.

A Review of Australian Tick Vaccine Research

Tick vaccine research in Australia has demonstrated leadership worldwide through the development of the first anti-tick vaccine in the 1990s. Australia’s Commonwealth Scientific and Industrial Research Organisation’s (CSIRO) research led to the development of vaccines and/or precursors of vaccines (such as crude extracts) for both the cattle tick and the paralysis tick. CSIRO commercialised the Bm86 vaccine in the early 1990s for Rhipicephalus australis; however, issues with dosing and lack of global conservation led to the market closure of Tick-GARD in Australia. New research programs arose both locally and globally. The Australian paralysis tick Ixodes holocyclus has perplexed research veterinarians since the 1920s; however, not until the 2000s did biotechnology exist to elucidate the neurotoxin—holocyclotoxin family of toxins leading to a proof of concept vaccine cocktail. This review revisits these discoveries and describes tributes to deceased tick vaccine protagonists in Australia, including Sir Clunies Ross, Dr Bernard Stone and Dr David Kemp.

Climatic suitability of the eastern paralysis tick, Ixodes holocyclus, and its likely geographic distribution in the year 2050

The eastern paralysis tick, Ixodes holocyclus is one of two ticks that cause potentially fatal tick paralysis in Australia, and yet information on the full extent of its present or potential future spatial distribution is not known. Occurrence data for this tick species collected over the past two decades, and gridded environmental variables at 1 km2 resolution representing climate conditions, were used to derive correlative ecological niche models to predict the current and future potential distribution. Several hundreds of candidate models were constructed with varying combinations of model parameters, and the best-fitting model was chosen based on statistical significance, omission rate, and Akaike Information Criterion (AICc). The best-fitting model matches the currently known distribution but also extends through most of the coastal areas in the south, and up to the Kimbolton peninsula in Western Australia in the north. Highly suitable areas are present around south of Perth, extending towards Albany, Western Australia. Most areas in Tasmania, where the species is not currently present, are also highly suitable. Future spatial distribution of this tick in the year 2050 indicates moderate increase in climatic suitability from the present-day prediction but noticeably also moderate to low loss of climatically suitable areas elsewhere.

The Efficacy of Ultrasonic Pest Repellent Devices against the Australian Paralysis Tick, Ixodes holocyclus (Acari: Ixodidae)

Ultrasonic pest repellers are often promoted as a means of protecting people and pets from the bites of hematophagous arthropods, such as ticks. However, to date, there has been no published research on the effectiveness of these devices against the Australian paralysis tick, Ixodes holocyclus Neumann. The purpose of this study was to test the effectiveness of nine ultrasonic devices against female I. holocyclus. Two arenas were constructed, one for the test (with the ultrasonic device) and one for the control (no device). Each arena had a test and an escape chamber, connected by a corridor. Twenty ticks were placed in each test chamber. After the ultrasonic device was operated for 1 h, the number of ticks in both chambers was recorded. Ten replicates were conducted for each device. The average number of ticks that moved from the test to the escape chamber was greater in all the test arenas, with three devices being statistically different from the control. However, the highest percent of ticks that escaped was only 19.5%. This amount is insufficient to offer adequate protection against tick bites and this study adds further weight to previous investigations that ultrasonic devices should not be employed in pest management.