A journey through virology, bacteriology, protozoology to ‘omics’ and commercialising anti-tick vaccines

How to navigate a career spanning from virology, bacteriology, protozoology, ticks, and flies is puzzling for most. However, common themes are present which mostly are associated with the application of basic immunology and molecular biology tools to solve animal health challenges. These included genotyping assays (ribotyping, PCR of genes with variable numbers of repeats), and diagnostic PCRs which have solved problems for industries by improving disease management such as: qPCR to detect Trichonomonas foetus (bovine VD) in reproductive tract clinical samples now used world-wide (commercialised by Thermofisher in 2011); genotyping Babesia bovis live parasites to demonstrate that the live vaccine had not reverted to virulence during a disease outbreak; qPCRs for bovine leukemia and bovine immune deficiency viruses to screen vaccine donor cattle; and the development of a PCR test to detect myiasis fly species exotic to Australia in fly traps in Northern Australia. My research Interest in gene function led to a fascination of RNA interference and elucidating this pathway in ticks. This led to a cattle tick vaccine research program through the Beef CRC (2005-2012) and the development of a reverse vaccinology pipeline based on an EST library of tick sequences (n=13,463). Following bioinformatics, ELISA and qPCR screening, we subsequently screened 80 candidate antibodies using a novel in vitro adult feeding model. After cattle trials using mixtures of B cell binding peptides, 20 were identified as potential vaccine candidates based on efficacies of 50-73% in cattle trials. From 2014-2021 the research has mostly been supported by Industry to undertake intensive cattle trial screening of candidates as individual peptides-KLH, multi-peptide plasmid constructs and 4 full recombinant proteins.  A recently concluded longevity trial using 2 initial boosts one month apart, immediate tick challenge and a second tick infestation 6 months after vaccination, yielded 2 final candidates in a vaccination mixture as whole recombinant proteins resulting in efficacies of 83% and 90% respectively. This result is a breakthrough as after the second tick infestation, the adult ticks were black with poor reproductive efficiency indicating that the tick infestations were boosting immunity and thus increasing the vaccine efficacy. Since 2012, we also extended our research to develop a vaccine for the Australian paralysis tick. Using transcriptomic analyses of adult female tick guts and salivary glands we identified a large family of holocyclotoxins/HTs (n=19). Following the screening of anti-sera used to treat canine paralysis, we identified 8 HTs and a proof of concept HT cocktail dog trial demonstrated protection from tick paralysis following challenge. Both vaccines are under further development to deliver products for uptake by the Australian pet industry (paralysis tick) and the global cattle industry (cattle tick).  Due to intellectual property sensitivities, these vaccine discoveries have not yet been published.