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Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

Saturday, 25th of March 2017

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

Nature. 2017 Feb 23;542(7642):445-449. doi: 10.1038/nature21060. Epub 2017 Feb 15.

Mordmüller B1, Surat G1, Lagler H1,2, Chakravarty S3, Ishizuka AS4, Lalremruata A1, Gmeiner M1, Campo JJ5, Esen M1, Ruben AJ3, Held J1, Calle CL1, Mengue JB1, Gebru T1, Ibáñez J1, Sulyok M1, James ER3, Billingsley PF3, Natasha KC3,6, Manoj A3, Murshedkar T3, Gunasekera A3, Eappen AG3, Li T3, Stafford RE3,6, Li M3,6, Felgner PL7, Seder RA4, Richie TL3, Sim BK3,6, Hoffman SL3, Kremsner PG1.

Author information

1 Institute of Tropical Medicine, University of Tübingen and replica breitling German Center for Infection Research, partner site Tübingen, 72074 Tübingen, Germany.

2 Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria.

3 Sanaria Inc., Rockville, Maryland 20850, USA.

4 Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.

5 Antigen Discovery Inc., Irvine, California 92618, USA.

6 Protein Potential, LLC, Rockville, Maryland 20850, USA.

7 Department of Medicine, University of California Irvine, Irvine, California 92697, USA.

Abstract

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 × 103 (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.