title: Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.
abstract: An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 × 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Andrew S
authors.identifier: 0000-0002-3024-7536
authors.initials: AS
authors.lastname: Ishizuka
authors.affiliation: Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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 (NIH), Maryland, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: DeZure
authors.affiliation: Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Berry
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
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 (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
authors.forename: Lee-Jah
authors.initials: LJ
authors.lastname: Chang
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Uzma N
authors.initials: UN
authors.lastname: Sarwar
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
authors.forename: LaSonji A
authors.initials: LA
authors.lastname: Holman
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Manoj
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.|Protein Potential, LLC, Rockville, Maryland, USA.
authors.forename: MingLin
authors.initials: M
authors.lastname: Li
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ruben
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Eappen
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.|Protein Potential, LLC, Rockville, Maryland, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Stafford
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.|Protein Potential, LLC, Rockville, Maryland, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: K C
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Tooba
authors.initials: T
authors.lastname: Murshedkar
authors.affiliation: Pharmaceutical Development Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hope
authors.initials: H
authors.lastname: DeCederfelt
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
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 (NIH), Maryland, USA.
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authors.initials: PJ
authors.lastname: Costner
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Jamie G
authors.initials: JG
authors.lastname: Saunders
authors.affiliation: Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Laurens
authors.affiliation: Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Flynn
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Whalen
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Todd
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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authors.initials: J
authors.lastname: Noor
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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authors.initials: S
authors.lastname: Rao
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Kailan
authors.initials: K
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authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Lynn
authors.affiliation: Naval Medical Research Center (NMRC), Malaria Department, Silver Spring, Maryland, USA.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Kemp
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Fahle
authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
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authors.initials: SA
authors.lastname: Mikolajczak
authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
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authors.initials: M
authors.lastname: Fishbaugher
authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
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authors.initials: BK
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authors.affiliation: Center for Infectious Disease Research, Seattle, Washington, USA.
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authors.initials: SH
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authors.affiliation: Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
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authors.initials: SA
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authors.affiliation: Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Garver
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
authors.affiliation: Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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authors.initials: BS
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authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.|Protein Potential, LLC, Rockville, Maryland, USA.
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.affiliation: Sanaria Inc., Rockville, Maryland, USA.
authors.forename: Stephen L
authors.initials: SL
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authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
authors.forename: Julie E
authors.initials: JE
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authors.affiliation: Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
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mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000071497:Immunogenicity, Vaccine / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D007371:Interferon-gamma