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Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity.
Mwakingwe-Omari, Agnes; Healy, Sara A; Lane, Jacquelyn; Cook, David M; Kalhori, Sahand; Wyatt, Charles; Kolluri, Aarti; Marte-Salcedo, Omely; Imeru, Alemush; Nason, Martha; Ding, Lei K; Decederfelt, Hope; Duan, Junhui; Neal, Jillian; Raiten, Jacob; Lee, Grace; Hume, Jen C C; Jeon, Jihyun E; Ikpeama, Ijeoma; Kc, Natasha; Chakravarty, Sumana; Murshedkar, Tooba; Church, L W Preston; Manoj, Anita; Gunasekera, Anusha; Anderson, Charles; Murphy, Sean C; March, Sandra; Bhatia, Sangeeta N; James, Eric R; Billingsley, Peter F; Sim, B Kim Lee; Richie, Thomas L; Zaidi, Irfan; Hoffman, Stephen L; Duffy, Patrick E.
Affiliation
  • Mwakingwe-Omari A; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Healy SA; Center for Vaccine Research, GlaxoSmithKline, Rockville, MD, USA.
  • Lane J; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Cook DM; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kalhori S; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Wyatt C; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kolluri A; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Marte-Salcedo O; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Imeru A; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Nason M; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ding LK; Biostatistical Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
  • Decederfelt H; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Duan J; Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA.
  • Neal J; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Raiten J; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lee G; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Hume JCC; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Jeon JE; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ikpeama I; Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA.
  • Kc N; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Chakravarty S; Sanaria, Rockville, MD, USA.
  • Murshedkar T; Protein Potential, Rockville, MD, USA.
  • Church LWP; Sanaria, Rockville, MD, USA.
  • Manoj A; Sanaria, Rockville, MD, USA.
  • Gunasekera A; Sanaria, Rockville, MD, USA.
  • Anderson C; Sanaria, Rockville, MD, USA.
  • Murphy SC; Sanaria, Rockville, MD, USA.
  • March S; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Bhatia SN; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • James ER; Department of Microbiology, University of Washington, Seattle, WA, USA.
  • Billingsley PF; Seattle Malaria Clinical Trials Center, Fred Hutch Cancer Research Center, Seattle, WA, USA.
  • Sim BKL; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA, USA.
  • Richie TL; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Zaidi I; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Hoffman SL; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.
  • Duffy PE; Broad Institute, Cambridge, MA, USA.
Nature ; 595(7866): 289-294, 2021 07.
Article in En | MEDLINE | ID: mdl-34194041
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Vaccines, Attenuated / Malaria Vaccines / Antibodies, Neutralizing / Liver Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Nature Year: 2021 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Vaccines, Attenuated / Malaria Vaccines / Antibodies, Neutralizing / Liver Type of study: Clinical_trials / Prognostic_studies Limits: Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Nature Year: 2021 Type: Article Affiliation country: United States