Vaccine Effort Targets Hookworm Larvae

James Cook University researchers will target proteins secreted by hookworm larvae as part of an international effort to develop a game-changing vaccine against the notorious parasite.

Recent clinical trials in Australia and Europe found patients vaccinated with irradiated hookworm larvae or repeated rounds of infection-treatment developed partial protection against hookworm infection, which affects almost half a billion people worldwide.

JCU molecular parasitologist Professor Alex Loukas said his team would now look at which larval antigens, or proteins, were recognised by the antibodies produced from the immune systems of those who were vaccinated with irradiated larvae.

"The antigens that American researchers are testing at the moment in clinical trials are produced by the adult stage of the hookworm, which lives in the gut. What we're now trying to do is identify the best antigens released by the larvae," he said.

"This is the stage that infects people through their skin and then migrates through your lungs. The research community agrees that any comprehensive vaccine against hookworm infection will need to contain multiple proteins so you can target different developmental phases of the hookworm with a single vaccination.

"So, we're trying to identify antigens released by the larvae that could be coupled in a vaccine with antigens released by the adult hookworm to see if you can induce antibodies to hit the parasite at multiple vulnerable points throughout its life history."

Those proteins most suitable for a vaccine would be recommended for further clinical development and eventual human trials.

"People don't naturally develop robust protective immunity to hookworms over time, so often it's the most elderly people in the community who are infected," Prof Loukas said.

"In a really heavy infection when you've got hundreds or thousands of worms, particularly in people who are already malnourished, people can become anaemic.

"And if you've got anaemia, you're unproductive and can't work. In children, they can suffer from stunted growth and intellectual disabilities."

While hookworm infections can be eradicated using over-the-counter medication, Dr Loukas said preventing re-infection was the challenge in impoverished tropical countries where the parasite thrived, such as Australia's closest northern neighbour, Papua New Guinea.

"People can take a drug to get rid of worms they have at the time, but then a few months later they'll get reinfected again," Prof Loukas said.

"That's why there's a push for a vaccine because it would provide long-lasting immunity."

The JCU team involves Prof Loukas, Dr Paul Giacomin and Dr Suchandan Sikder, as well as Masters of Science student Eti Sarkar and PhD student Tamara Thomas.

The JCU team is one year into a five-year European Union-funded project under the research and innovation programme Horizon Europe.

The project, known as WORMVACS2.0, is led by Leiden University Medical Centre in the Netherlands and involves research institutes, universities and companies from Europe, Africa and the United States.

As an associated partner of the project, the JCU team aims to produce a prototype hookworm vaccine, with any relevant larval proteins identified to then undergo systematic testing by their colleagues in Europe.

To learn more about the WORMVACS2.0 project, head to www.wormvacs.org

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