Single-Dose Malaria Vaccine Offers Unprecedented 90% Protection?

After one week in Kenya volunteering to help maintain a Masai village water scheme, I have heard no mention of malaria, nor seen, never mind being bitten by, a mosquito. So I will address a paper highlighted in news-medical.net ‘Single immunization with genetically attenuated PfΔmei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial’ by Roozen et al at Leiden, Netherlands published in Nature Medicine. The paper was listed two weeks ago in Malaria World.

In this double-blind placebo study fifteen malaria-naive participants aged 15–30 years were enrolled at Leiden University Medical Centre, Leiden. They were vaccinated by being bitten 50 (±5) times with GA2-infected (10 test subjects) or uninfected Anopheles (5 control subjects). Six weeks later, all participants underwent controlled human malaria infection (CHMI) through the bites of five mosquitos infected with unattenuated homologous wild-type Pf parasites. In subsequent visits they found that 9 of 10 (90%) participants in the GA2-MB group were fully protected against Pf malaria and remained PfqPCR-negative until day 28 post-CHMI. By contrast, all participants in the placebo group became parasitaemic (log-rank test P < 0.0001). This is using a PCR amplification technique.

However, there was no notable difference in symptoms between either group at any stage, so while the technique does prove that the test subjects dosed with a vaccine administered with 50 mosquito bites by mosquitos infected with genetically attenuated Pf sporozoites, were less likely to have wild Pf sporozoites in their blood than control patients who suffered 50 bites by uninfected Anopheles stephensi mosquitos. They were no more likely to become ill. But I would not expect healthy young Dutch adults to become ill, unless also malnourished or poisoned.

The test mosquitos were infected using a membrane technique (reference Ponnudurai et al 1989 – behind paywall) in which mosquitos in a jar can ‘feed’ on the test blood through a membrane (see image), which had the genetically modified plasmodium added.

As the authors admit, the study is limited by the small sample size of healthy malaria-naive participants who do not adequately represent the target population for malaria vaccines in endemic areas. And administration of GA2 through mosquito bites is not a feasible method for large-scale immunization campaigns.

This study is a remarkable scientific endeavour. And IF malaria is an infectious disease caused by a plasmodium germ transmitted by mosquito bites, this might be a breakthrough against malaria. However, this is far from certain and based on the assumption of the validity of germ theory instead of terrain theory for the occurrence of disease.

Picture from UNC Medical website.