Biomedical Engineering Reference
In-Depth Information
8.4 Concluding Remarks
Proteolytic activity has been identified in the extracts of numerous helminth
parasites, and the enzymes responsible have been given more attention than any
other protein family because of the crucial roles they play in parasitism. In
particular, secreted proteases have been shown to be indispensable facilitators of
key processes, including nutrient acquisition and tissue migration, and are con-
sidered prime vaccine targets due to their exposure to the host immune system.
Promising candidates have been discussed in this chapter and include aspartic
and cysteine proteases from gastrointestinal nematodes of humans and livestock.
Where explored, the ecacy of these vaccines seems to be due to the generation of
antibodies that bind to the parasite-derived target enzyme and inhibit its enzy-
matic function, compromising essential aspects of parasite biology.
Hematophagous helminths have similar pathobiologies, not least of which is
their obligate requirement for blood, and so have developed similar pathways
and use homologous/orthologous proteases to achieve their ends. This implies
that homologs of molecules of known vaccine ecacy might prove similarly
ecacious from one parasite to another and can even cross-protect between
helminths. Recent evidence of this includes the protective ecacy of aspartic
and cysteine protease orthologues of N. americanus and A. caninum,in
homologous and heterologous models of hookworm infection. 2,3,20
The emergence of drug-resistant parasites and the limited sustainability of
drug-administration programs in endemic areas 52,53 have provided great
incentive for the development of molecular vaccines for helminth infections.
Proteases represent the group of proteins for which the most success in helm-
nith vaccinology has been achieved, and the achievements reported herein offer
exciting future prospects for development of immune therapies to control and
eradicate these debilitating parasites.
Acknowledgments
We are grateful to the following organizations for funding our research: National
Health andMedical Research Council of Australia (NHMRC), Bill andMelinda
Gates Foundation via a grant to the Sabin Vaccine Institute and the Australian
Research Council. MP and NR are recipients of NHMRC CJ Martin training
awards, and AL is the recipient of an NHMRC senior research fellowship.
References
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