Malaria parasites invading a red blood cell (Image: Dr Paul Gilson)
Burnet Institute researchers have created a malaria ‘Frankenstein’ to reveal secrets about the deadly species Plasmodium vivax in a major milestone to advance the development of a world-first life-saving malaria vaccine.
The research team led by Professor James Beeson and Dr Damien Drew effectively tricked a different malaria species, Plasmodium falciparum, into expressing a P. vivax protein.
The team was surprised and excited to find that antibodies generated by vaccination to the P. vivax protein effectively blocked infection of human red blood cells, revealing a new vaccine target and an entirely new strategy for malaria vaccine development.
“It’s very difficult to study vivax in the laboratory because you can’t easily grow it or manipulate it genetically, or understand its molecular interactions, and that’s been a big barrier to developing vaccines,” Professor Beeson said.
“Our strategy was to get around this problem by using P. falciparum, which we can do a lot with in the laboratory, and trick it into expressing P. vivax proteins – it’s a bit like a Frankenstein of an organism that we’ve created.
“We basically got P. falciparum and genetically modified it to make it like P. vivax and that’s enabled us to study how P. vivax infects human red blood cells and develop vaccines.”
Despite decades of global research and development, no malaria vaccine has ever been licensed, and very little progress has been made in developing vaccines for P. vivax malaria, despite its enormous global importance.
Plasmodium vivax and P. falciparum are the deadliest of the five species of malaria that infect humans, accounting for almost all of the estimated 212 million cases globally and 429,000 deaths in 2015, according to the latest World Health Organization (WHO) data.
The Burnet study, published in the Journal of Infectious Diseases, focused on AMA1, a key protein shared by P. vivax and P. falciparum.
While it was well known that AMA1 plays a key role in helping P. falciparum to infect red blood cells, much about the function and molecular properties of P. vivax AMA1 have been unclear.
The research showed the function of AMA1 in both species to be complementary despite the fact that P. falciparum and P. vivax evolved independently and otherwise differ in the proteins they use to infect human red blood cells.
“This was a remarkable and unexpected result,” Professor Beeson said.
“The primary focus of our work was on P. vivax, but it also sheds light on a vaccine for P. falciparum because this critical protein is common to both and has a lot more flexibility in the way it can function than we’d anticipated.
“It’s a significant step forward and it’s opened up new ways of developing vaccines which is a high priority globally.”
WHO and the global community have set ambitious malaria elimination targets, with many countries in the Asia Pacific region aiming for elimination by 2030.
The latest WHO data suggests, however, that the longer-term decline in the burden of malaria this century may have stalled over the past three years because of mounting challenges including an increase in drug resistance.
“So we really need a vaccine to achieve that goal of malaria elimination,” Professor Beeson said.