Sporozoite immunization: innovative translational science to support the fight against malaria.
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Richie Thomas L, Church L W Preston, Murshedkar Tooba, Billingsley Peter F, James Eric R, Chen Mei-Chun, Abebe Yonas, K C Natasha, Chakravarty Sumana, Dolberg David, Healy Sara A, Diawara Halimatou, Sissoko Mahamadou S, Sagara Issaka, Cook David M, Epstein Judith E, Mordmüller Benjamin, Kapulu Melissa, Kreidenweiss Andrea, Franke-Fayard Blandine, Agnandji Selidji T, López Mikue María-Silvia A, McCall Matthew B B, Steinhardt Laura, Oneko Martina, Olotu Ally, Vaughan Ashley M, Kublin James G, Murphy Sean C, Jongo Said, Tanner Marcel, Sirima Sodiomon B, Laurens Matthew B, Daubenberger Claudia, Silva Joana C, Lyke Kirsten E, Janse Chris J, Roestenberg Meta, Sauerwein Robert W, Abdulla Salim, Dicko Alassane, Kappe Stefan H I, Sim B Kim Lee, Duffy Patrick E, Kremsner Peter G, Hoffman Stephen L
Аннотация
AREAS COVERED: Sporozoites (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 OPINION: First 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.
UNLABELLED: Introduction Malaria, 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 covered Sporozoites (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 opinion First 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.