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.
Highlights
Immunization with Plasmodium falciparum (Pf) sporozoites under chemoprophylaxis (PfSPZCVac) is the most efficacious approach to malaria vaccination
It was shown in previous trials that immunization with whole-cell sporozoites, either radiationattenuated (PfSPZ Vaccine)[7,8,9,10,11] or chemoattenuated by the concomitant administration of an antimalarial (PfSPZ chemoprophylaxis vaccine, PfSPZ-CVac)[12,13,14], is highly immunogenic and induces robust protection against homologous straincontrolled human malaria infection (CHMI)
In our previous PfSPZ-CVac trial TÜCHMI-002 (NCT02115516), we showed that direct venous inoculation (DVI) administration of three doses of 5.12 × 104 PfSPZ Challenge over 8 weeks under weekly chloroquine (CQ) chemoprophylaxis protected 100% (9/9) of study participants against CHMI conducted with the homologous strain of Pf and performed 10 weeks after immunization[12]
Summary
Immunization with Plasmodium falciparum (Pf) sporozoites under chemoprophylaxis (PfSPZCVac) is the most efficacious approach to malaria vaccination. It was shown in previous trials that immunization with whole-cell sporozoites, either radiationattenuated (PfSPZ Vaccine)[7,8,9,10,11] or chemoattenuated by the concomitant administration of an antimalarial (PfSPZ chemoprophylaxis vaccine, PfSPZ-CVac)[12,13,14], is highly immunogenic and induces robust protection against homologous (vaccine) straincontrolled human malaria infection (CHMI). In our previous PfSPZ-CVac trial TÜCHMI-002 (NCT02115516), we showed that direct venous inoculation (DVI) administration of three doses of 5.12 × 104 PfSPZ Challenge (infectious PfSPZ) over 8 weeks under weekly chloroquine (CQ) chemoprophylaxis protected 100% (9/9) of study participants against CHMI conducted with the homologous (vaccine) strain of Pf and performed 10 weeks after immunization[12]. These results indicated that shorter regimens with fewer doses of CQ could be used, potentially at the cost of reduced VE
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