Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity

Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane, David M. Cook, Sahand Kalhori, Charles Wyatt, Aarti Kolluri, Omely Marte-Salcedo, Alemush Imeru, Martha Nason, Lei K. Ding, Hope Decederfelt, Junhui Duan, Jillian Neal, Jacob Raiten, Grace Lee, Jen C. C. Hume, Jihyun E. Jeon, Ijeoma Ikpeama, Natasha Kc, Sumana Chakravarty, Tooba Murshedkar, L. W. Preston Church, Anita Manoj, Anusha Gunasekera, Charles Anderson, Sean C. Murphy, Sandra March, Sangeeta N. Bhatia, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie, Irfan Zaidi, Stephen L. Hoffman and Patrick E. Duffy ()
Additional contact information
Agnes Mwakingwe-Omari: National Institutes of Health
Sara A. Healy: National Institutes of Health
Jacquelyn Lane: National Institutes of Health
David M. Cook: National Institutes of Health
Sahand Kalhori: National Institutes of Health
Charles Wyatt: National Institutes of Health
Aarti Kolluri: National Institutes of Health
Omely Marte-Salcedo: National Institutes of Health
Alemush Imeru: National Institutes of Health
Martha Nason: National Institute of Allergy and Infectious Diseases
Lei K. Ding: National Institutes of Health
Hope Decederfelt: National Institutes of Health
Junhui Duan: National Institutes of Health
Jillian Neal: National Institutes of Health
Jacob Raiten: National Institutes of Health
Grace Lee: National Institutes of Health
Jen C. C. Hume: National Institutes of Health
Jihyun E. Jeon: National Institutes of Health
Ijeoma Ikpeama: Clinical Center, National Institutes of Health
Natasha Kc: Sanaria
Sumana Chakravarty: Sanaria
Tooba Murshedkar: Sanaria
L. W. Preston Church: Sanaria
Anita Manoj: Sanaria
Anusha Gunasekera: Sanaria
Charles Anderson: National Institutes of Health
Sean C. Murphy: University of Washington
Sandra March: Massachusetts Institute of Technology
Sangeeta N. Bhatia: Massachusetts Institute of Technology
Eric R. James: Sanaria
Peter F. Billingsley: Sanaria
B. Kim Lee Sim: Sanaria
Thomas L. Richie: Sanaria
Irfan Zaidi: National Institutes of Health
Stephen L. Hoffman: Sanaria
Patrick E. Duffy: National Institutes of Health

Nature, 2021, vol. 595, issue 7866, 289-294

Abstract: Abstract The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))—which kill liver-stage and blood-stage parasites, respectively—and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.

Date: 2021
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DOI: 10.1038/s41586-021-03684-z

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