15 Feb 2017

Malaria vaccines need forethought in development

The malaria parasite, Plasmodium falciparum, amidst the
blood cells. Image: Aku Analis
by Anne Crawford

Monash University infectious diseases researchers have called for a new approach to malaria vaccine development, criticising those developing malaria vaccines that fail to act on the parasite’s polymorphism – or ability to change form.

Malaria kills almost 500,000 people a year globally and can have a crippling economic effect on the countries in which it is endemic. Some 3.2 billion people live in areas where they are at risk of malaria. No commercially available vaccine exists to prevent the disease.

Professor Magdalena Plebanski and Dr Katie Flanagan, from the Department of Immunology and Pathology’s Vaccine and Infectious Diseases Unit, say in a review published in the high-impact journal Trends in Parasitology that current malaria vaccines that have progressed to human trials largely fail to provide broad-spectrum protection against different polymorphic parasite variants.

This includes RTS,S, the most advanced vaccine candidate against the deadliest form of human malaria, Plasmodium falciparum. Even if they work perfectly, most such vaccines can only eliminate a fraction of the parasite variants circulating in a population, Professor Plebanski said.

“A second important point that is currently not considered is that the effects of vaccines go beyond the specific protection provided against the one disease they are designed to protect against – and can influence, either beneficially or otherwise – the way the body handles other unrelated diseases,” she said.

“A malaria vaccine, as well as giving protection against malaria, may also impact overall morbidity and mortality in the target human population.”

These non-specific effects (NSEs) of vaccines need to be better understood, the paper says.

Vaccine developers who do not fully consider the eventual outcomes of a vaccine early in the developmental process may find it financially prohibitive to redesign the vaccine once it has progressed down the long and costly regulatory and human trial pathway, it says.

The researchers advocate a holistic approach from the start of vaccine development, with more early basic research – such as the incorporation of antigens designed to offer broad protection across many polymorphic targets, and evaluating potential vaccine non-specific effects – before work progresses to commercial development.

Vaccines targeting malaria in endemic areas would need to have unique new properties, they maintain.

The development of vaccines could benefit from breakthroughs in the treatment of other diseases such as cancer immunotherapy, as well as through using new tools in nanotechnology, information technology and chemical engineering, the researchers say.

Plebanski M, Flanagan KL. The Economics of Malaria Vaccine Development. Trends Parasitol. 2017 Feb 3. pii: S1471-4922(17)30006-5. doi: 10.1016/j.pt.2017.01.006. [Epub ahead of print]

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