Novel malaria vaccine candidate gives strong, lasting protection
According to the study published, yesterday, in the journal Nature, by A. Mwakingwe-Omari et al and titled ‘Two chemo-attenuated PfSPZ malaria vaccines induce sterile hepatic immunity’, the vaccine combines live parasites with either of two widely used antimalarial drugs- an approach termed chemoprophylaxis vaccination.
The researchers said a Phase 2 clinical trial of the vaccine is now underway in Mali, a malaria-endemic country. If the approach proves successful there, chemoprophylaxis vaccination, or CVac, potentially could help reverse the stalled decline of global malaria. Currently, there is no vaccine in widespread use for the mosquito-transmitted disease.
The trials were conducted at the United States National Institutes of Health (NIH) Clinical Centre in Bethesda, Maryland.
Patrick E. Duffy, M.D., of the NIH National Institute of Allergy and Infectious Diseases (NIAID), and Stephen L. Hoffman, M.D., CEO of Sanaria Inc., Rockville, Maryland, led them.
The Sanaria vaccine, called PfSPZ, is composed of sporozoites, the form of malaria parasite transmitted to people by mosquito bites. Sporozoites travel through the blood to the liver to initiate infection. In the CVac trials, healthy adult volunteers received PfSPZ along with either pyrimethamine, a drug that kills liver-stage parasites, or chloroquine, which kills blood-stage parasites. Three months later, under carefully controlled conditions, the volunteers were exposed to either an African malaria parasite strain that was the same as that in the vaccine (homologous challenge) or a variant South American parasite (heterologous challenge) that was more genetically distant from the vaccine strain than hundreds of African parasites. Exposure in both cases was via inoculation into venous blood, which infects all unvaccinated individuals.
At the lowest PfSPZ dosage, the CVac approach conferred modest protection: only two of nine volunteers (22.2 per cent) who received the pyrimethamine combination were protected from homologous challenge. In contrast, seven out of eight volunteers (87.5 per cent) who received the highest PfSPZ dosage combined with pyrimethamine were protected from homologous challenge, and seven out of nine volunteers (77.8 per cent) were protected from heterologous challenge.
In the case of the chloroquine combination, all six volunteers (100 per cent) who received the higher PfSPZ dosage were completely protected from heterologous challenge. The high levels of cross-strain protection lasted at least three months (the time elapsed between vaccination and challenge) for both higher-dose regimens.
The authors noted that one hundred per cent protection for three months against heterologous variant parasites is unprecedented for any malaria vaccine in development.
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