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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Sterile protection against human malaria by chemoattenuated PfSPZ vaccine
Nature, Volume 542, No. 7642, Year 2017
Notification
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Description
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 × 104 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 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Authors & Co-Authors
Mordmüller, Benjamin G.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Surat, Guzin
Germany, Tubingen
Eberhard Karls Universität Tübingen
Lagler, Heimo
Germany, Tubingen
Eberhard Karls Universität Tübingen
Austria, Vienna
Medizinische Universität Wien
Chakravarty, Sumana
United States, Rockville
Sanaria Inc.
Ishizuka, Andrew S.
United States, Bethesda
National Institutes of Health Nih
Lalremruata, Albert
Germany, Tubingen
Eberhard Karls Universität Tübingen
Gmeiner, Markus
Germany, Tubingen
Eberhard Karls Universität Tübingen
Campo, Joseph J.
United States, Irvine
Antigen Discovery Inc.
Esen, Meral
Germany, Tubingen
Eberhard Karls Universität Tübingen
Ruben, Adam J.
United States, Rockville
Sanaria Inc.
Held, Jana
Germany, Tubingen
Eberhard Karls Universität Tübingen
Calle, Carlos Lamsfus
Germany, Tubingen
Eberhard Karls Universität Tübingen
Mengue, Juliana Boex
Germany, Tubingen
Eberhard Karls Universität Tübingen
Woldearegai, Tamirat Gebru
Germany, Tubingen
Eberhard Karls Universität Tübingen
Ibáñez, Javier
Germany, Tubingen
Eberhard Karls Universität Tübingen
Sulyok, Mihály
Germany, Tubingen
Eberhard Karls Universität Tübingen
James, Eric Robinson
United States, Rockville
Sanaria Inc.
Billingsley, Peter F.
United States, Rockville
Sanaria Inc.
Kc, Natasha
United States, Rockville
Sanaria Inc.
United States, Rockville
Protein Potential Llc
Manoj, Anita
United States, Rockville
Sanaria Inc.
Murshedkar, Tooba
United States, Rockville
Sanaria Inc.
Gunasekera, Anusha Munasinghe
United States, Rockville
Sanaria Inc.
Li, Tao
United States, Rockville
Sanaria Inc.
Li, Minglin
United States, Rockville
Sanaria Inc.
United States, Rockville
Protein Potential Llc
Felgner, Philip Louis
United States, Irvine
University of California, Irvine
Seder, Robert A.
United States, Bethesda
National Institutes of Health Nih
Richie, Thomas L.
United States, Rockville
Sanaria Inc.
Sim, Betty Kim Lee
United States, Rockville
Sanaria Inc.
United States, Rockville
Protein Potential Llc
Hoffman, Stephen L.
United States, Rockville
Sanaria Inc.
Kremsner, Peter G.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Statistics
Citations: 272
Authors: 30
Affiliations: 7
Identifiers
Doi:
10.1038/nature21060
ISSN:
00280836
Research Areas
Cancer
Infectious Diseases
Maternal And Child Health