Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial.

Autor: Sulyok Z; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Fendel R; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany. rolf.fendel@uni-tuebingen.de.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany. rolf.fendel@uni-tuebingen.de., Eder B; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Lorenz FR; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Kc N; Sanaria Inc, Rockville, MD, USA., Karnahl M; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Lalremruata A; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Nguyen TT; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Held J; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Adjadi FAC; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Klockenbring T; Fraunhofer Institute of Molecular Biology and Applied Ecology IME, Aachen, Germany., Flügge J; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Woldearegai TG; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Lamsfus Calle C; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Ibáñez J; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Rodi M; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Egger-Adam D; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Kreidenweiss A; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Köhler C; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Esen M; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Sulyok M; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany., Manoj A; Sanaria Inc, Rockville, MD, USA., Richie TL; Sanaria Inc, Rockville, MD, USA., Sim BKL; Sanaria Inc, Rockville, MD, USA., Hoffman SL; Sanaria Inc, Rockville, MD, USA., Mordmüller B; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Kremsner PG; Institute of Tropical Medicine, University and University Hospital of Tübingen, Tübingen, Germany.; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 May 04; Vol. 12 (1), pp. 2518. Date of Electronic Publication: 2021 May 04.
DOI: 10.1038/s41467-021-22740-w
Abstrakt: Immunization with Plasmodium falciparum (Pf) sporozoites under chemoprophylaxis (PfSPZ-CVac) is the most efficacious approach to malaria vaccination. Implementation is hampered by a complex chemoprophylaxis regimen and missing evidence for efficacy against heterologous infection. We report the results of a double-blinded, randomized, placebo-controlled trial of a simplified, condensed immunization regimen in malaria-naive volunteers (EudraCT-Nr: 2018-004523-36). Participants are immunized by direct venous inoculation of 1.1 × 10 5 aseptic, purified, cryopreserved PfSPZ (PfSPZ Challenge) of the PfNF54 strain or normal saline (placebo) on days 1, 6 and 29, with simultaneous oral administration of 10 mg/kg chloroquine base. Primary endpoints are vaccine efficacy tested by controlled human malaria infection (CHMI) using the highly divergent, heterologous strain Pf7G8 and safety. Twelve weeks following immunization, 10/13 participants in the vaccine group are sterilely protected against heterologous CHMI, while (5/5) participants receiving placebo develop parasitemia (risk difference: 77%, p = 0.004, Boschloo's test). Immunization is well tolerated with self-limiting grade 1-2 headaches, pyrexia and fatigue that diminish with each vaccination. Immunization induces 18-fold higher anti-Pf circumsporozoite protein (PfCSP) antibody levels in protected than in unprotected vaccinees (p = 0.028). In addition anti-PfMSP2 antibodies are strongly protection-associated by protein microarray assessment. This PfSPZ-CVac regimen is highly efficacious, simple, safe, well tolerated and highly immunogenic.
Databáze: MEDLINE
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