Malaria’s genetic poker-playing could threaten GlaxoSmithKline’s Mosquirix vaccine

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Malaria parasite could reshuffle its genes to evade one's immune system, a finding that could redirect vaccine development.

Malaria parasites can shuffle genes, creating different strains in different people and eluding the immune system in the process. The phenomenon, unearthed in a new study, could put the efficacy of GlaxoSmithKline’s vaccine Mosquirix, among others, into question.

A study involving 641 children aged 1 to 12 years living in a small village in the African country of Gabon found that each child carried a different strain of the P. falciparum parasite, each with a different combination of about 60 “var genes” responsible for encoding surface antigens.

In short, the parasite evolved with enormous genetic diversity, researchers said.

“This structure allows each parasite to look different to the immune system, and provides the possibility for the malaria parasite to keep re-infecting the same people,” similar to but much more complicated than flu, said Karen Day, professor of population science at the University of Melbourne and the study’s lead author, in a release.

The study was conducted by scientists at the University of Melbourne, the University of Chicago and others from the Netherlands and France. Its findings were published in the Proceedings of the National Academy of Sciences.

The “strain theory” was first raised by Sunetra Gupta and Day in 1990s, proposing that malaria has a vast genetic variation. The study in Gabon was just a preliminary validation of the hypothesis, and researchers are now conducting genetic fingerprinting and modeling malaria strains in larger human populations.

If the theory is correct, as the study suggests, it would trigger a “significant revision of the theory of malaria control,” which is currently based on “a genetically homogeneous parasite population,” instead of variant antigens.

That means current malaria vaccines efforts, pioneered by GSK’s first-of-its-kind Mosquirix, might not work as well as hoped. Previous studies have already shown that Mosquirix’s efficacy could dwindle significantly at year four of vaccination. That data led to the World Health Organization’s decision to test the shot in a real-world pilot program before a full rollout. Ghana, Kenya and Malawi have been chosen to carry the study starting next year.

But GSK seems confident in Mosquirix's capability. In a statement sent to FiercePharma, GSK recognized malaria's genetic diversity as a well-known phenomenon and that overcoming the parasite's defense mechanism is “extraordinarily challenging.” Although it did not explicitly say whether Mosquirix could tackle different strains of malaria, the British drugmaker held its ground by pointing to the vaccine's phase 3 results—45% protection after 18 months of vaccination and 36% at four years.

“Given the huge number of cases of malaria, we believe that the potential of this vaccine to reduce the burden of disease in sub-Saharan Africa is significant,” a spokesperson said in the statement.

More than 20 malaria vaccine candidates are currently in advanced preclinical or clinical development, the WHO said last May.