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

: Sulyok, Z.; Fendel, R.; Eder, B.; Lorenz, F.-R.; Kc, N.; Karnahl, M.; Lalremruata, A.; Nguyen, T.T.; Held, J.; Adjadi, F.A.C.; Klockenbring, Torsten; Flügge, J.; Woldearegai, T.G.; Lamsfus Calle, C.; Ibáñez, J.; Rodi, M.; Egger-Adam, D.; Kreidenweiss, A.; Köhler, C.; Esen, M.; Sulyok, M.; Manoj, A.; Richie, T.L.; Sim, B.K.L.; Hoffman, S.L.; Mordmüller, B.; Kremsner, P.G.

Volltext urn:nbn:de:0011-n-6364709 (961 KByte PDF)
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Erstellt am: 26.8.2021

Nature Communications 12 (2021), Art. 2518, 10 S.
ISSN: 2041-1723
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IME ()

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.