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, 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
Author Information
  1. Thomas L Richie: Sanaria Inc, Rockville, MD, USA. ORCID
  2. L W Preston Church: Sanaria Inc, Rockville, MD, USA. ORCID
  3. Tooba Murshedkar: Sanaria Inc, Rockville, MD, USA.
  4. Peter F Billingsley: Sanaria Inc, Rockville, MD, USA. ORCID
  5. Eric R James: Sanaria Inc, Rockville, MD, USA. ORCID
  6. Mei-Chun Chen: Sanaria Inc, Rockville, MD, USA.
  7. Yonas Abebe: Sanaria Inc, Rockville, MD, USA.
  8. Natasha Kc: Sanaria Inc, Rockville, MD, USA.
  9. Sumana Chakravarty: Sanaria Inc, Rockville, MD, USA.
  10. David Dolberg: Sanaria Inc, Rockville, MD, USA.
  11. Sara A Healy: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ORCID
  12. Halimatou Diawara: Malaria Research and Training Center, Mali-NIAID ICER, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
  13. Mahamadou S Sissoko: Malaria Research and Training Center, Mali-NIAID ICER, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. ORCID
  14. Issaka Sagara: Malaria Research and Training Center, Mali-NIAID ICER, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. ORCID
  15. David M Cook: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ORCID
  16. Judith E Epstein: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ORCID
  17. Benjamin Mordmüller: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. ORCID
  18. Melissa Kapulu: Biosciences Department, Kenya Medical Research Institute KEMRI-Wellcome Research Programme, Kilifi, Kenya. ORCID
  19. Andrea Kreidenweiss: Institut für Tropenmedizin, Universitätsklinikum Tübingen, Tübingen, Germany. ORCID
  20. Blandine Franke-Fayard: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. ORCID
  21. Selidji T Agnandji: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. ORCID
  22. María-Silvia A López Mikue: Ministry of Health and Social Welfare, Government of Equatorial Guinea, Malabo, Equatorial Guinea.
  23. Matthew B B McCall: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. ORCID
  24. Laura Steinhardt: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. ORCID
  25. Martina Oneko: Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya. ORCID
  26. Ally Olotu: Bagamoyo Research and Training Center, Ifakara Health Institute, Bagamoyo, Tanzania. ORCID
  27. Ashley M Vaughan: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. ORCID
  28. James G Kublin: Department of Global Health, University of Washington, Seattle, WA, USA. ORCID
  29. Sean C Murphy: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. ORCID
  30. Said Jongo: Bagamoyo Research and Training Center, Ifakara Health Institute, Bagamoyo, Tanzania.
  31. Marcel Tanner: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. ORCID
  32. Sodiomon B Sirima: Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso. ORCID
  33. Matthew B Laurens: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA. ORCID
  34. Claudia Daubenberger: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. ORCID
  35. Joana C Silva: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. ORCID
  36. Kirsten E Lyke: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA. ORCID
  37. Chris J Janse: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. ORCID
  38. Meta Roestenberg: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. ORCID
  39. Robert W Sauerwein: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. ORCID
  40. Salim Abdulla: Bagamoyo Research and Training Center, Ifakara Health Institute, Bagamoyo, Tanzania.
  41. Alassane Dicko: Malaria Research and Training Center, Mali-NIAID ICER, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. ORCID
  42. Stefan H I Kappe: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. ORCID
  43. B Kim Lee Sim: Sanaria Inc, Rockville, MD, USA. ORCID
  44. Patrick E Duffy: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ORCID
  45. Peter G Kremsner: Institut für Tropenmedizin, Universitätsklinikum Tübingen, Tübingen, Germany. ORCID
  46. Stephen L Hoffman: Sanaria Inc, Rockville, MD, USA. ORCID

Abstract

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 (Pf), the deadliest human malaria parasite.
AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by 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.

Keywords

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Grants

  1. /Wellcome Trust
  2. CC999999/Intramural CDC HHS
  3. R01 AI141900/NIAID NIH HHS
  4. ZIA AI001170/Intramural NIH HHS

MeSH Term

Pregnancy
Child
Animals
Humans
Female
Sporozoites
Translational Science, Biomedical
Malaria Vaccines
Vaccines, Attenuated
Malaria
Malaria, Falciparum
Plasmodium falciparum
Immunization

Chemicals

Malaria Vaccines
Vaccines, Attenuated

Word Cloud

Created with Highcharts 10.0.0PfSPZmalariavaccinesAfrica000PfgenerationefficaciouschildrenpregnantwomenhighlyvaccinehumanparasiteSporozoitesefficacyinfectionreviewtrials'safeCHMIsafetyVaccineINTRODUCTION:Malariadevastatingfebrileillnesscausedprotozoanparasitessickened247people2021killed619mostlysub-SaharaneffectiveurgentlyneededespeciallydeadliestAREASCOVERED:SPZstagetransmittedmosquitoeshumansimmunogenachieving >90%describes >30clinicalUSAEuropeAsiabasedfirst-handknowledgePubMedsearches'sporozoites'malaria'vaccines'EXPERTOPINION:Firstradiation-attenuatedwelltolerated80-100%homologouscontrolledprovide18-19 monthsprotectionwithoutboostingSecondchemo-attenuatedpotent100%stringentheterologousvariantstrainrequireco-administereddrugraisingconcernsThirdlateliverstage-arrestingreplicationcompetentLARCgenetically-attenuatedexpectedOverallmeettolerabilityrequirementsprotectingtravelersexposedlicensurepopulationspossiblewithin5yearsProtectingmassvaccinationprogramsblocktransmissioneliminatelong-termobjectivesSporozoiteimmunization:innovativetranslationalsciencesupportfightPfSPZ-CVacPfSPZ-LARC2Plasmodiumfalciparum

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