دورية أكاديمية
Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.
العنوان: | Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. |
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المؤلفون: | Mordmüller B; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Surat G; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Lagler H; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany.; Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria., Chakravarty S; Sanaria Inc., Rockville, Maryland 20850, USA., Ishizuka AS; Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA., Lalremruata A; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Gmeiner M; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Campo JJ; Antigen Discovery Inc., Irvine, California 92618, USA., Esen M; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Ruben AJ; Sanaria Inc., Rockville, Maryland 20850, USA., Held J; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Calle CL; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Mengue JB; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Gebru T; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Ibáñez J; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., Sulyok M; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany., James ER; Sanaria Inc., Rockville, Maryland 20850, USA., Billingsley PF; Sanaria Inc., Rockville, Maryland 20850, USA., Natasha KC; Sanaria Inc., Rockville, Maryland 20850, USA.; Protein Potential, LLC, Rockville, Maryland 20850, USA., Manoj A; Sanaria Inc., Rockville, Maryland 20850, USA., Murshedkar T; Sanaria Inc., Rockville, Maryland 20850, USA., Gunasekera A; Sanaria Inc., Rockville, Maryland 20850, USA., Eappen AG; Sanaria Inc., Rockville, Maryland 20850, USA., Li T; Sanaria Inc., Rockville, Maryland 20850, USA., Stafford RE; Sanaria Inc., Rockville, Maryland 20850, USA.; Protein Potential, LLC, Rockville, Maryland 20850, USA., Li M; Sanaria Inc., Rockville, Maryland 20850, USA.; Protein Potential, LLC, Rockville, Maryland 20850, USA., Felgner PL; Department of Medicine, University of California Irvine, Irvine, California 92697, USA., Seder RA; Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA., Richie TL; Sanaria Inc., Rockville, Maryland 20850, USA., Sim BK; Sanaria Inc., Rockville, Maryland 20850, USA.; Protein Potential, LLC, Rockville, Maryland 20850, USA., Hoffman SL; Sanaria Inc., Rockville, Maryland 20850, USA., Kremsner PG; Institute of Tropical Medicine, University of Tübingen and German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany. |
المصدر: | Nature [Nature] 2017 Feb 23; Vol. 542 (7642), pp. 445-449. Date of Electronic Publication: 2017 Feb 15. |
نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Malaria Vaccines/*immunology , Malaria, Falciparum/*immunology , Malaria, Falciparum/*prevention & control , Plasmodium falciparum/*immunology , Vaccines, Attenuated/*immunology, Adolescent ; Adult ; Antibodies, Protozoan/blood ; Antibodies, Protozoan/immunology ; Chloroquine/therapeutic use ; Double-Blind Method ; Healthy Volunteers ; Humans ; Immunologic Memory/immunology ; Malaria Vaccines/administration & dosage ; Malaria, Falciparum/blood ; Malaria, Falciparum/parasitology ; Middle Aged ; Plasmodium falciparum/classification ; Sporozoites/immunology ; T-Lymphocytes/immunology ; Time Factors ; Vaccines, Attenuated/administration & dosage ; Young Adult |
مستخلص: | A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 10 4 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 10 3 (group I) or 1.28 × 10 4 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 10 4 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas. |
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معلومات مُعتمدة: | R44 AI066791 United States AI NIAID NIH HHS; R44 AI058375 United States AI NIAID NIH HHS; R44 AI134500 United States AI NIAID NIH HHS; R43 AI058375 United States AI NIAID NIH HHS; R43 AI055229 United States AI NIAID NIH HHS; R44 AI055229 United States AI NIAID NIH HHS; T32 GM145449 United States GM NIGMS NIH HHS; T32 GM007171 United States GM NIGMS NIH HHS; 5R44AI058375 United States AO NIAID NIH HHS |
المشرفين على المادة: | 0 (Antibodies, Protozoan) 0 (Malaria Vaccines) 0 (Vaccines, Attenuated) 886U3H6UFF (Chloroquine) |
تواريخ الأحداث: | Date Created: 20170216 Date Completed: 20170718 Latest Revision: 20240303 |
رمز التحديث: | 20240303 |
مُعرف محوري في PubMed: | PMC10906480 |
DOI: | 10.1038/nature21060 |
PMID: | 28199305 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4687 |
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DOI: | 10.1038/nature21060 |