Research highlights

Read a selection of articles about our recent parasitic diseases research.

Novel vaccine approaches for protecting against helminth parasites

Contributors: Mali Camberis, Dr Marina Harvie, Shiau-Choot Tang, Melanie Prout, Rachel Hunter, Prof Graham Le Gros, collaborating with Brett Delahunt (Wellington School of Medicine & Health Sciences) and Dr William Paul (NIH, USA)

Vaccination is currently viewed as the only long-term solution to preventing human hookworm infection. However, the cell types, tissues, effector molecules and cytokines that mediate protective immunity against helminth parasites, and are the key to a good vaccine, remain largely undefined. Previous work from Prof Graham Le Gros' laboratory using knockout models and the rodent hookworm Nippostrongylus brasiliensis, identified MHC Class II, STAT6 and IL-4 as important immunological parameters for generating protection in the lung. 

They are now extending this work by examining the role of basophils in protective immunity using IL-3 knockout models, as well as looking at the involvement of the innate cytokines IL25, RelmA and RelmB. 

In a recent study Prof Le Gros and colleagues discovered that the immune cells resident in the lung are critical for establishing protective immunity against tissue migrating hookworm larvae. These findings open novel areas of research in protective immunity against helminth parasites.

Scientists make breakthrough in fight against hookworm parasite

Human hookworm infection is currently controlled through frequent use of antihelminthic drugs in school-age children, however, high rates of re-infection occur soon after treatment and there is evidence of emerging drug resistance.

”Vaccination is currently viewed as the only longterm solution for reducing the enormous burden this disease imposes on developing countries,” says Prof Graham Le Gros.

“Before we can start developing a vaccine against the parasite, we first need to identify the immune mechanisms that can protect against hookworm infection.”

Using a rodent model of human hookworm infection called Nippostrongylus brasiliensis, Prof Le Gros’ research team showed that the lung was the critical site for establishing immunity against parasite infection.

“Our findings imply that for a vaccine to be effective it must target the immune cells resident in the lung and stimulate a specific kind of immune response that we have yet to discover.”

In 2010 the Health Research Council of New Zealand granted $1.2 million to Prof Le Gros to further develop this pioneering research. The outcome of which could alleviate suffering and economic stalemate for over one billion people worldwide.

Harvie M, Camberis M, Tang SC, Delahunt B, Paul W, Le Gros G (2010) The lung is an important site for priming CD4 T-cellmediated protective immunity against gastrointestinal helminth parasites. Infect Immun, 78:3753-62

 

Dissecting the Th2 immune responses to Nippostrongylus brasiliensis infection

Of all the microbial infections relevant to mammals the relationship between parasitic worms and what constitutes and regulates a host protective immune response is perhaps the most complex and evolved. Nippostrongylus brasiliensis is a tissue migrating parasitic roundworm of rodents. Immune competent hosts respond to infection by N. brasiliensis with a rapid and selective development of a profound Th2 immune response that appears able to confer life long protective immunity against reinfection.

“Identification of the processes, cells and cytokines that regulate the Th2 responses to tissue parasites such as N. brasiliensis is proving exciting but controversial,” says Professor Graham Le Gros. “There are increasing numbers of studies that seek to tease apart the specific components of this fascinating process.”

“Our own research has identified the lung as a site of protective immunity against reinfection with N. brasiliensis,” says Professor Le Gros. “Using the latest gene knockout and reporter mice technologies, we have been able to undertake a careful and thorough investigation of the cellular and molecular cues stimulated by the parasite to coordinate these Th2 immune responses.”

The above research is summarised in context of what is known internationally in an invited review for Frontiers in Immunology.

Harvie M, Camberis M, Le Gros G (2013) Development of CD4 T cell dependent immunity against N. brasiliensis infection. Front Immunol, 4:74 (Invited review)