Sporozoite immunization: innovative translational science to support the fight against malaria.
Richie TL., Church LWP., Murshedkar T., Billingsley PF., James ER., Chen M-C., Abebe Y., Natasha Kc None., Chakravarty S., Dolberg D., Healy SA., Diawara H., Sissoko MS., Sagara I., Cook DM., Epstein JE., Mordmüller B., Kapulu M., Kreidenweiss A., Franke-Fayard B., Agnandji ST., López Mikue M-SA., McCall MBB., Steinhardt L., Oneko M., Olotu A., Vaughan AM., Kublin JG., Murphy SC., Jongo S., Tanner M., Sirima SB., Laurens MB., Daubenberger C., Silva JC., Lyke KE., Janse CJ., Roestenberg M., Sauerwein RW., Abdulla S., Dicko A., Kappe SHI., Sim BKL., Duffy PE., Kremsner PG., Hoffman SL.
IntroductionMalaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite.Areas coveredSporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.'Expert opinionFirst generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.