Burnet Senior Postdoctoral Research Officer, Dr Damien Drew

Burnet Institute scientists have used genetically modified malaria to identify key variants, which are predominantly recognised by people living in malaria-endemic areas, to inform the development of a potential vaccine.

The research project, published in BMC Medicine, focused on a potential vaccine candidate AMA1, an antigen capable of inducing an immune response to the malaria parasite, Plasmodium falciparum.

“It’s been known for a long time that people who live in areas where malaria is endemic have antibodies to AMA1, and lots of studies have shown that there’s an association between people having antibodies to AMA1 and a reduced incidence of malaria,” lead author Dr Damien Drew said.

“But one of the issues with AMA1 is that it’s highly variable, so the AMA1 that’s present in a new infection may be slightly different from the one they’ve had previously, so a pre-existing immunity to AMA1 may not protect you from the next infection.

“The aim of this paper was to see whether naturally exposed populations have antibodies to AMA1, and then to see how cross-protective those antibodies were.”

The research involved the development of new functional assays to provide more detailed information than was previously available about the magnitude of the antibodies, as well as the types of antibodies that are relevant to providing protection.

“What we can do now is look at making recombinant forms of AMA1 to generate antibodies, and then come back and test how cross inhibitory these antibodies are to different strains,” Dr Drew said.

“We’ve identified what we think are four key variants which could generate a potentially cross-protective vaccine, so what we’re looking at now is ways of making those proteins in an efficient manner which can then progress into production.

“If you can make a vaccine cocktail with these four variants which gives you cross-inhibition against 25 wild-type strains and it gives you a high level of antibody, then that’s a good starting point for the next phase of a trial.”

Click here to download the BMC Medicine research article ‘A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens’.