New malaria vaccine effective in clinical trial

In collaboration with the biotech company Sanaria Inc., University of Tübingen researchers have demonstrated in a clinical trial that a new vaccine for malaria called Sanaria® PfSPZ-CVac has been up to 100 per cent effective when assessed at ten weeks after its last dose. For the trial, Professor Peter Kremsner and Dr Benjamin Mordmüller of the Institute of Tropical Medicine and the German Center for Infection Research (DZIF) in Tübingen used malaria parasites provided by Sanaria. The vaccine incorporated fully viable – not weakened or otherwise inactivated – malaria pathogens together with the medication to combat them. Their research results have been published in the latest edition of Nature.

Malaria parasites are transmitted by the bite of female Anopheles mosquitoes. The Plasmodium falciparum parasite is responsible for most malaria infections and almost all deaths caused by the disease world-wide. The majority of the vaccines tried previously involved the use of individual molecules found in the pathogen. However, they were unable to provide sufficient immunity to the disease.

The Tübingen study involved 67 healthy adult test persons, none of whom had previously had malaria. The best immune response was shown in a group of nine test persons who received the highest dose of the vaccine three times at four-week intervals. At the end of the trial, all nine of these individuals had 100 per cent protection from the disease.

Vaccinating with live malaria parasites

“That protection was probably caused by specific T-lymphocytes and antibody responses to the parasites in the liver,” remsner explained. The researchers analysed the body’s immune reactions and identified protein patterns which would enable further improvements in malaria vaccines, he added. The researchers injected live malaria parasites into the test subjects, at the same time preventing the development of the disease by adding chloroquine – which has been used to treat malaria for many years. This enabled the researchers to exploit the behaviour of the parasites and the properties of chloroquine.

Once the person is infected, the Plasmodium falciparum parasite migrates to the liver to reproduce. During its incubation period there, the human immune system could respond, but at this stage, the pathogen does not make the person sick. On top of that, chloroquine does not take effect in the liver – so it is unable to prevent the parasite from reproducing. Malaria only breaks out when the pathogen leaves the liver, entering the bloodstream and going into the red corpuscles, where it continues to reproduce and spread. As soon as the pathogen enters the bloodstream, however, it can be killed by chloroquine – and the disease cannot break out.

“By vaccinating with a live, fully active pathogen, it seems clear that we were able to set off a very strong immune response,” said study leader Mordmüller. “Additionally, all the data we have so far indicate that what we have here is relatively stable, long-lasting protection.” He explained that in the group of test persons who demonstrated 100 per cent protection after receiving a high dose three times, protection was reliably still in place after ten weeks – and remained measurable for even longer. He added that the new vaccine showed no adverse effects on the test persons.

The next step is to further test the vaccine’s effectiveness over several years in a clinical study in Gabon funded by DZIF. Malaria is one of the biggest health threats in this African nation. The University of Tübingen has worked with the Albert Schweitzer Hospital in the Gabonese town of Lambaréné and with the neighbouring research institute, the Centre de Recherches Médicales de Lambaréné, for many years.

(University Tübingen/wi)

Further information: WHO
 
Publication: Benjamin Mordmüller, Peter G. Kremsner: et al.: Sterile protection against human malaria by chemoattenuated PfSPZ vaccine, Nature, 
DOI: 10.1038/nature21060