Hookworm discovery at Malaghan Institute

Hookworm: The Great infection of Mankind, discovery at Malaghan Institute

Professor Graham Le Gros has led a team which has stimulated both innate and memory responses to the parasite, discovering along the way the unexpected behaviour of one particular immune cell, in Hookworm, one of the world’s most devastating tropical diseases affecting 1 billion1 people. The journal, Nature Communications, has today published the research2.

1 Fenwick A (March 2012). "The global burden of neglected tropical diseases.". Public health 126 (3): 233–6. doi:10.1016/j.puhe.2011.11.01

2 View the journal article online at:

DOI: 10.1038/ncomms7970 |www.nature.com/naturecommunications

Ten years of work has seen the Wellington-based scientists demonstrate the interaction between innate and adaptive immune cells, never seen before, providing a credible platform for researchers to work towards preventing a disease that causes global suffering.

Hookworm affects mostly the poorest billion people in the world and, according to the World Health Organisation, contributes to the cycle of poverty and ill health for communities of people living on less than $2 a day. Hookworm infection causes childhood and maternal anaemia, wasting, pain, disability and impaired brain development, but has proved impossible to eradicate as rates of reinfection are high.

Hookworms reproduce in the gut and the eggs passed in stools. The cycle of reinfection continues in poor communities where the lack of both sanitation and footwear makes eradication impossible. The most feasible way to break this cycle would be to create a vaccine for protective immunity but before we can start developing a vaccine against the parasite however, we first need to identify the immune mechanisms that can best protect against hookworm infection.

Graham Le Gros explains, “Humans have evolved to develop immunity to many parasites, but not Hookworm. An unusual feature of their life cycle is that it includes migration of the larvae to the lungs before they develop into adults in the gut.

We were able to create an immune response in the lungs of mice that made it hard for the parasite to live – and therefore break the lifecycle. Our hunt is now to find the right hookworm protein to combine with an adjuvant triggering the activation of these immune cells - to teach a human body to have a memory of how to fight Hookworm.”

Additionally, the team demonstrated one immune cell - type 2 innate lymphoid cells ( ILC2s) - trigger immunity and work with other immune cells, the Macrophages and T helper cells. Previously ILC2s were not thought to be involved as an effector cell in long term memory response to fight off the disease.

The research was assisted by synthetic chemist Dr Gavin Painter from the Ferrier Research Institute at Victoria University of Wellington. The Ferrier Institute are regular collaborators with scientists from the Malaghan Institute. The work was funded by the Health Research Council of New Zealand.

About the Malaghan Institute of Medical Research

We are here to make a difference to people’s lives and health while contributing to New Zealand’s economy and scientific community. Our scientists believe that the key to making this difference lies in the immune system; the body’s own natural defence against disease.

We are a registered charity, and our pioneering research programmes are reliant on support from the community, the corporate sector, trusts, and contestable grants; through organisations like the Health Research Council of New Zealand.

Last year we patented a novel vaccine technology to prevent asthma. Research is ongoing to translate it into a human application.

Earlier in 2015 a team jointly led by Malaghan Institute and Griffiths University discovered a world first demonstrated mitochondrial DNA movement between cells in cancer cells, a world first. The research lays important groundwork for understanding human diseases other than cancer, since defective mitochondrial DNA is known to account for around 200 diseases and is implicated in many more. It could also usher in a new field where synthetic mitochondrial DNA is custom-designed to replace defective genes.

Independent clinicians are currently trialling a therapeutic Melanoma vaccine developed at the Malaghan Institute. None of the clinicians and researchers involved can comment publicly until this process has been completed. That way we can be sure the findings are true to our scientific principles.

ENDS

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