Helminth vaccines: from mining genomic information for vaccine targets to systems used for protein expression

• Published in: International Journal for Parasitology 2003-05, Vol.33 (5), p.621-640
• Main Authors: Dalton, John P, Brindley, Paul J, Knox, Dave P, Brady, Ciaran P, Hotez, Peter J, Donnelly, Sheila, O'Neill, Sandra M, Mulcahy, Grace, Loukas, Alex
• Format: Article
• Language: English
• Subjects: Animals; DNA, Circular - analysis; Endopeptidases - genetics; Escherichia coli - genetics; Expression system; Fermentation - genetics; Gene Expression - genetics; Genes, Helminth - genetics; Genome; Genomics; Helminth; Helminthiasis - genetics; Helminthiasis - prevention & control; Helminthiasis, Animal - genetics; Helminthiasis, Animal - prevention & control; Helminths - genetics; Humans; Insecta - genetics; Parasite; Protease; Recombinant protein; Recombinant Proteins - genetics; Vaccine; Vaccines - therapeutic use; Yeasts - genetics
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/S0020-7519(03)00057-2

The control of helminth diseases of people and livestock continues to rely on the widespread use of anti-helminthic drugs. However, concerns with the appearance of drug resistant parasites and the presence of pesticide residues in food and the environment, has given further incentive to the goal of discovering molecular vaccines against these pathogens. The exponential rate at which gene and protein sequence information is accruing for many helminth parasites requires new methods for the assimilation and analysis of the data and for the identification of molecules capable of inducing immunological protection. Some promising vaccine candidates have been discovered, in particular cathepsin L proteases from Fasciola hepatica, aminopeptidases from Haemonchus contortus, and aspartic proteases from schistosomes and hookworms, all of which are secreted into the host tissues or into the parasite intestine where they play important roles in host-parasite interactions. Since secreted proteins, in general, are exposed to the immune system of the host they represent obvious candidates at which vaccines could be targeted. Therefore, in this article, we consider the potential values and uses of algorithms for characterising cDNAs amongst the collated helminth genomic information that encode secreted proteins, and methods for their selective isolation and cloning. We also review the variety of prokaryotic and eukaryotic cell expression systems that have been employed for the production and downstream purification of recombinant proteins in functionally active form, and provide an overview of the parameters that must be considered if these recombinant proteins are to be commercialised as vaccine therapeutics in humans and/or animals.