Metazoan Parasite Vaccines: Present Status and Future Prospects

Abstract

Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while also continuously expanding into non-endemic countries. Combined with the ever growing number of reports on drug-resistance and the lack of effective treatment programs for many metazoan diseases, the impact that these organisms will have on quality of life remain a global challenge. Vaccination as an effective prophylactic treatment has been demonstrated for well over 200 years for bacterial and viral diseases. From the earliest variolation procedures to the cutting edge technologies employed today, many protective preparations have been successfully developed for use in both medical and veterinary applications. In spite of the successes of these applications in the discovery of subunit vaccines against prokaryotic pathogens, not many targets have been successfully developed into vaccines directed against metazoan parasites. With the current increase in -omics technologies and metadata for eukaryotic parasites, target discovery for vaccine development can be expedited. However, a good understanding of the host/vector/pathogen interface is needed to understand the underlying biological, biochemical and immunological components that will confer a protective response in the host animal. Therefore, systems biology is rapidly coming of age in the pursuit of effective parasite vaccines. Despite the difficulties, a number of approaches have been developed and applied to parasitic helminths and arthropods. This review will focus on key aspects of vaccine development that require attention in the battle against these metazoan parasites, as well as successes in the field of vaccine development for helminthiases and ectoparasites. Lastly, we propose future direction of applying successes in pursuit of next generation vaccines.

Keywords: OMICS techniques; antigen identification; parasite control; parasites; systems biology; vaccine development; vaccines.

Figure 1

Diagrammatic workflow for identification and evaluation of next generation metazoan vaccine candidates adapted from Haçariz and Sayers (2016). In wet-lab conditions, the parasite of interest is treated to ensure isolation of appropriate factors involved in parasite biology and parasite-host interactions, providing data on genomics, transcriptomics, proteomics, lipidomics, glycomics, and metabolomics levels. During “dry lab” applications, the various parasite components can be analyzed and functionally annotated using various functional and reverse genetics techniques. By employing large-scale techniques and bioinformatics tools, exposed targets able to elicit a host immune response can be preferentially selected and their protective epitopes predicted for improved vaccine design. These targets can enter process developmental stages where antigens are produced and tested in small-scale experimental vaccination trials. Subsequent improvements of protective antigens include vaccine formulation, stability and efficacy during process development, prior to extensive clinical and field trail evaluations. Dashed lines indicate some additional loops for antigen discovery, functional annotation and vaccine improvement and asterisks feedback information from metabolomics studies. cGMP, Current good manufacturing practices; GO, gene ontology; HRFTMS, Fourier transform mass spectrometry; KEGG, Kyoto Encyclopedia of Genes and Genomes; LC-MS/MS, Liquid chromatography-tandem mass spectrometry; MS, mass spectrometry; NMR, Nuclear magnetic resonance; PLGS, ProteinLynx Global; PNGase F, Peptide-N-Glycosidase F; QC, Quality control.

Figure 2

An integrated strategy for parasite and parasite-borne disease control. Several tools are available for management of metazoan parasites (purple), the associated pathogens that can be transmitted (red) and the host animal (green). For metazoan parasite control, pesticides are the most prevalent control measure currently implemented. Resistance to chemical control is a concern that has led to the development of diagnostic tests to identify resistant populations, as well as biological control methods such as bio-pesticides, sterile parasite techniques and pheromones (Yadav et al., 2017). For disease control, treatments are available for most pathogens. Early diagnosis and reports of new and/or resistant pathogenic strains are essential to limit the impact of outbreaks. Some control measures for hosts (human and animal) has involved breeding of resistant stock and/or maintaining endemic stability. Several key areas are currently a priority focus of ongoing research efforts (orange tabs) and these include understanding the host defense against infection/infestation, development of the next generation of vaccines (and diagnostics) and understanding the biology of transmitted pathogens to identify new targets for treatment and diagnosis.