The Sanaria vaccine, called PfSPZ, combines live malaria parasites with one of two existing antimalarial drugs and could be the breakthrough in developing an effective and lasting vaccine.
Malaria. Image Credit: nechaevkon/Shutterstock.com
Durable protection from malaria even after 3 months post-vaccination
As of 2019, there were an estimated 229 million cases of malaria worldwide with 409 000 deaths. This prevalent disease is caused by parasites transmitted by infected female Anopheles mosquitoes and can be life-threatening.
To date, people in known malaria-infected regions can take one of 2 antimalarial treatments. Clinical research on malaria has focused on developing an effective vaccine, yet recent developments have had little long-term efficacy.
However, researchers have now developed a promising vaccine candidate. The new vaccine called PfSPZ is now under U.S. Phase 1 clinical trials and has demonstrated unprecedentedly high levels of durable protection when volunteers were later exposed to disease-causing malaria parasites.
This vaccine is based on a chemoprophylaxis method combining live parasites with either of two widely used antimalarial drugs. The injection of live parasites gives the immune system of recipients the ability to identify and eliminate the parasites effectively, as in any other vaccine. However, the use of antimalarial drugs boosts the immune system in combatting the parasites injected.
Specifically, the live parasites are the sporozoites of the malaria parasite that travel through the bloodstream to the liver to initiate infection. The antimalarial drugs pyrimethamine, a drug that kills liver-stage parasites, and chloroquine, which kills blood-stage parasites, were also combined within the vaccine.
Trials were undertaken for the vaccine at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland, and were led by Patrick E. Duy, M.D., of the NIH National Institute of Allergy and Infectious Disease s(NIAID), and Stephen L. Homan, M.D., CEO of Sanaria Inc., Rockville, Maryland. The results are published in the journal Nature.
Healthy adult volunteers received PfSPZ along with either pyrimethamine, or chloroquine, and were then infected three months later under controlled conditions with either an African malaria parasite strain that was the same as that in the vaccine or a variant South American parasite that was more genetically distant from the vaccine strain.
The vaccine at the lowest dosage conferred only modest protection as expected with 22.2% of patients who received the pyrimethamine combination were protected from the African malarial variant challenge.
Contrastingly, 87.5% of patients who received the highest PfSPZ dosage combined with pyrimethamine were protected from the same variant and 77.8% were protected from the South American variant.
In addition to the first combination, of the patients injected with the chloroquine combination 100% dosage were completely protected from the South American variant.
Most promisingly, the high levels of cross-strain protection lasted at least three months for both higher-dose regimens, with 100% protection for three months against the South American variant parasites.
Unprecedented results with promising future fighting against malaria
The authors noted that the results of this clinical trial are unprecedented for any malaria vaccine in development. Indeed, the data suggests that the chemoprophylaxis approach of combining live parasites and drug treatments could be a promising technique for vaccination.
This may provide a key breakthrough for vaccine development, providing key protection for residents living in malaria-endemic regions as well as travelers.
Further clinical trials with larger sample sizes, different treatment combinations, and dosage concentrations, will provide further insight into the effectiveness of this method. Nevertheless, other vaccine efforts may also benefit from using the chemoprophylaxis strategy to develop effective and long-term protection in the future.
- Mwakingwe-Omari, A., Healy, S.A., Lane, J. et al. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity. Nature (2021). https://doi.org/10.1038/s41586-021-03684-z