Expert Review of Vaccines (Dec 2023)

Sporozoite immunization: Innovative Translational Science to Support the Fight against malaria

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

DOI
https://doi.org/10.1080/14760584.2023.2245890
Journal volume & issue
Vol. 0, no. 0

Abstract

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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, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

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