1. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity
- Author
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Sumana Chakravarty, Eric R. James, Stephen L. Hoffman, Lei K. Ding, Jillian Neal, Charles Wyatt, Sahand Kalhori, Anita Manoj, Alemush Imeru, Omely Marte-Salcedo, Sangeeta N. Bhatia, Hope Decederfelt, David M. Cook, Agnes Mwakingwe-Omari, Martha Nason, Jen C. C. Hume, Sara A. Healy, Aarti Kolluri, Natasha Kc, Ijeoma Ikpeama, B. Kim Lee Sim, Peter F. Billingsley, Sean C. Murphy, L. W. Preston Church, Jihyun E. Jeon, Sandra March, Grace K. Lee, Irfan Zaidi, Jacob Raiten, Junhui Duan, Anusha Gunasekera, Thomas L. Richie, Tooba Murshedkar, Jacquelyn Lane, Patrick E. Duffy, and Charles Anderson
- Subjects
Adult ,Male ,0301 basic medicine ,Time Factors ,T-Lymphocytes ,Plasmodium falciparum ,030231 tropical medicine ,Heterologous ,Enzyme-Linked Immunosorbent Assay ,Vaccines, Attenuated ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Chloroquine ,Malaria Vaccines ,parasitic diseases ,medicine ,Animals ,Humans ,Life Cycle Stages ,Multidisciplinary ,biology ,Vaccination ,Middle Aged ,biology.organism_classification ,medicine.disease ,Vaccine efficacy ,Antibodies, Neutralizing ,Virology ,Malaria ,030104 developmental biology ,Pyrimethamine ,Liver ,Immunoglobulin G ,Antibody Formation ,Female ,medicine.drug - 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. Two malaria vaccines comprising Plasmodium falciparum sporozoites and treatment with either pyrimethamine or chloroquine induced durable protective responses against both the African vaccine strain and a heterologous South American strain of P. falciparum.
- Published
- 2021