Novel Chemoattenuated PfSPZ Malaria Vaccines Demonstrate Potent and Durable Protection in Phase 1 Trials

July 4, 2021 /BIOON/ -- Currently, the decline in global malaria incidence has stalled, which perhaps underscores the need to develop vaccines capable of inducing durable sterilizing immunity. Recently, an article published in an international journalNatureIn the aforementioned research report titled "Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity",Scientists from institutions including the pharmaceutical company GlaxoSmithKline have developed a novel malaria vaccine through research that provides robust and durable protection.

Image source: https://www.nature.com/articles/s41586-021-03684-z

Researchers reported that results from two Phase 1 clinical trials conducted in the United States using this novel candidate malaria vaccine revealed that the regimen confers an unprecedented high level of sustained protection when volunteers are subsequently exposed to pathogenic malaria parasites. This novel vaccine, termed chemoprophylaxis vaccination (CVac), combines a live parasite with two widely used antimalarial drugs, and researchers are currently conducting Phase 2 clinical trials of the vaccine in Mali, a malaria-endemic country. If this vaccine strategy proves successful in the region, CVac could potentially reverse the stagnation in global malaria prevention and control, given that no vaccine is currently widely used for the prevention of mosquito-borne diseases.

The Sanaria vaccine, known as PfSPZ, consists of sporozoites, the parasitic form transmitted to humans through mosquito bites. Sporozoites travel via the bloodstream to the liver, where they initiate infection. In the Cvac trial, healthy adult volunteers received the PfSPZ vaccine concurrently with either pyrimethamine, a drug that kills liver-stage parasites, or chloroquine, a drug that kills blood-stage parasites.Three months later, under carefully controlled conditions, volunteers were exposed to either the same African *Plasmodium* strain as in the vaccine (homologous challenge) or a variant South American parasite (heterologous challenge), the latter being genetically more distant from the vaccine strain than hundreds of African parasites. In both cases, exposure was administered via intravenous inoculation, which would infect all unvaccinated control subjects.

Two chemically attenuated PfSPZ vaccines can induce sterile hepatic immunity.

Image source: Mwakingwe-Omari, et al.Nature (2021).doi：10.1038/s41586-021-03684-z

At the lowest dose of PfSPZ, the Cvac regimen conferred modest protection, with 2 of 9 volunteers (22.2%) who received the pyrimethamine combination regimen protected against homologous challenge. In contrast, 7 of 8 volunteers (87.5%) who received the highest dose of PfSPZ with pyrimethamine were protected against homologous challenge, whereas 7 of 9 volunteers (77.8%) were protected against heterologous challenge. Under the chloroquine combination regimen, all 6 volunteers (100%) who received the highest dose of PfSPZ were protected against heterologous challenge. The high-level cross-strain protection afforded by both high-dose regimens persisted for at least three months, corresponding to the interval between vaccination and challenge.

In summary,Researchers noted that, for any malaria vaccine under development, achieving 100% protection against heterologous variant parasites for three months is unprecedented; the data from this study indicate that CVac may represent the most promising vaccination approach for travelers to malaria-endemic regions and populations residing in these areas..(Bioon.com)

Original Source:

Mwakingwe-Omari, A., Healy, S.A., Lane, J. et al. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity. Nature (2021).doi：10.1038/s41586-021-03684-z