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

Zita Sulyok, Rolf Fendel (), Bianca Eder, Freia-Raphaella Lorenz, Natasha Kc, Matthias Karnahl, Albert Lalremruata, The T. Nguyen, Jana Held, Folashade Almeine Cyntiche Adjadi, Torsten Klockenbring, Judith Flügge, Tamirat Gebru Woldearegai, Carlos Lamsfus Calle, Javier Ibáñez, Miriam Rodi, Diane Egger-Adam, Andrea Kreidenweiss, Carsten Köhler, Meral Esen, Mihály Sulyok, Anita Manoj, Thomas L. Richie, B. Kim Lee Sim, Stephen L. Hoffman, Benjamin Mordmüller and Peter G. Kremsner
Additional contact information
Zita Sulyok: University and University Hospital of Tübingen
Rolf Fendel: University and University Hospital of Tübingen
Bianca Eder: University and University Hospital of Tübingen
Freia-Raphaella Lorenz: University and University Hospital of Tübingen
Natasha Kc: Sanaria Inc
Matthias Karnahl: University and University Hospital of Tübingen
Albert Lalremruata: University and University Hospital of Tübingen
The T. Nguyen: University and University Hospital of Tübingen
Jana Held: University and University Hospital of Tübingen
Folashade Almeine Cyntiche Adjadi: University and University Hospital of Tübingen
Torsten Klockenbring: Fraunhofer Institute of Molecular Biology and Applied Ecology IME
Judith Flügge: University and University Hospital of Tübingen
Tamirat Gebru Woldearegai: University and University Hospital of Tübingen
Carlos Lamsfus Calle: University and University Hospital of Tübingen
Javier Ibáñez: University and University Hospital of Tübingen
Miriam Rodi: University and University Hospital of Tübingen
Diane Egger-Adam: University and University Hospital of Tübingen
Andrea Kreidenweiss: University and University Hospital of Tübingen
Carsten Köhler: University and University Hospital of Tübingen
Meral Esen: University and University Hospital of Tübingen
Mihály Sulyok: University and University Hospital of Tübingen
Anita Manoj: Sanaria Inc
Thomas L. Richie: Sanaria Inc
B. Kim Lee Sim: Sanaria Inc
Stephen L. Hoffman: Sanaria Inc
Benjamin Mordmüller: University and University Hospital of Tübingen
Peter G. Kremsner: University and University Hospital of Tübingen

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract 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 × 105 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.

Date: 2021
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DOI: 10.1038/s41467-021-22740-w

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