title: Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.
abstract: A live-attenuated malaria vaccine,Plasmodium falciparumsporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) withPlasmodium falciparum(Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 105PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P= 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.
authors.affiliation: Center for Vaccine Development and Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Andrew S
authors.identifier: 0000-0002-3024-7536
authors.initials: AS
authors.lastname: Ishizuka
authors.affiliation: Center for Vaccine Development and Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Berry
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Adam
authors.initials: A
authors.lastname: DeZure
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Anita
authors.initials: A
authors.lastname: Manoj
authors.affiliation: Sanaria Inc., Rockville, MD 20850.|Protein Potential LLC, Rockville, MD 20850.
authors.forename: Minglin
authors.initials: M
authors.lastname: Li
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ruben
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Eappen
authors.affiliation: Sanaria Inc., Rockville, MD 20850.|Protein Potential LLC, Rockville, MD 20850.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Stafford
authors.affiliation: Sanaria Inc., Rockville, MD 20850.|Protein Potential LLC, Rockville, MD 20850.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kc
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Tooba
authors.initials: T
authors.lastname: Murshedkar
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Floreliz H
authors.initials: FH
authors.lastname: Mendoza
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ingelise J
authors.initials: IJ
authors.lastname: Gordon
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Zephir
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: LaSonji A
authors.initials: LA
authors.lastname: Holman
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Plummer
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Hendel
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Laura
authors.initials: L
authors.lastname: Novik
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Pamela J M
authors.initials: PJ
authors.lastname: Costner
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jamie G
authors.initials: JG
authors.lastname: Saunders
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Berkowitz
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Flynn
authors.affiliation: Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.affiliation: Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Garver
authors.affiliation: Center for Vaccine Development and Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Laurens
authors.affiliation: Center for Vaccine Development and Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: Sanaria Inc., Rockville, MD 20850.|Protein Potential LLC, Rockville, MD 20850.
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.affiliation: Sanaria Inc., Rockville, MD 20850.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; rseder@mail.nih.gov.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity; D034101:Sporozoites / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D017780:Malaria Vaccines; D014613:Vaccines, Attenuated
keywords: T-cell immunology; live-attenuated vaccine; malaria; plasmodium; sporozoite