Abstract
ABSTRACT.Plasmodium falciparum sporozoite (PfSPZ) Vaccine is composed of radiation-attenuated, aseptic, purified cryopreserved PfSPZ. Multiple clinical trials empirically assessing two to six doses have shown multi-dose priming (two to four doses the first week) to be optimal for protection in both 4- and 16-week regimens. In this randomized, double-blind, normal saline (NS) placebo-controlled trial, four groups (G) of 18- to 32-year-old Equatoguineans received multi-dose priming regimens with or without a delayed final dose at 4 or 16 weeks. The regimens were G1: days 1, 3, 5, 7, and 113; G2: days 1, 3, 5, and 7; G3: days 1, 3, 5, 7, and 29; and G4: days 1, 8, and 29. All doses were 9 × 105 PfSPZ. Tolerability, safety, immunogenicity, and vaccine efficacy (VE) against homologous controlled human malaria infection (CHMI) 6–7 weeks after vaccination were assessed to down-select the best regimen. All four regimens were safe and well tolerated, with no significant differences in adverse events (AEs) between vaccinees (N = 84) and NS controls (N = 20) or between regimens. Out of 19 controls, 13 developed Pf parasitemia by quantitative polymerase chain reaction (qPCR) after CHMI. Only the vaccine regimen administered on study days 1, 8, and 29 gave significant protection (7/21 vaccinees versus 13/19 controls infected, VE 51.3%, P = 0.03, Barnard’s test, two-tailed). There were no significant differences in antibodies against Pf circumsporozoite protein (PfCSP), a major SPZ antigen, between protected and nonprotected vaccinees or controls pre-CHMI. The six controls not developing Pf parasitemia had significantly higher antibodies to blood stage antigens Pf exported protein 1 (PfEXP1) and Pf merozoite surface protein 1 (PfMSP1) than the controls who developed parasitemia, suggesting naturally acquired immunity against Pf limited infections in controls. This study identified a safe, protective, 4-week, multi-dose prime vaccination regimen for assessment in future trials of PfSPZ Vaccine.
Highlights
Malaria continues to be a major global health problem, with the WHO African Region reporting 215 million cases (94% of the global burden) in 2019
Vaccine efficacy (VE) . 90% against homologous controlled human malaria infection (CHMI) at 3–11 weeks after last dose has been shown in the United States,3,5 Tanzania,11 and Mali,17 and can last for at least 14 months
Vaccinees in each group were well balanced with respect to age and body mass index (BMI) when compared with each of the other groups or the pooled control groups (Supplemental Table 1)
Summary
Malaria continues to be a major global health problem, with the WHO African Region reporting 215 million cases (94% of the global burden) in 2019. SanariaVR PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved, whole Plasmodium falciparum (Pf) sporozoites (SPZ), is designed to achieve these objectives. Plasmodium falciparum sporozoites Vaccine has been assessed in 21 completed or ongoing trials in the United. 90% against homologous (same parasite strain in vaccine and challenge) controlled human malaria infection (CHMI) at 3–11 weeks after last dose has been shown in the United States, Tanzania, and Mali, and can last for at least 14 months.. In field studies, during 24 weeks of follow-up post-vaccination in three trials in Mali and one in Burkina Faso, VE against first episode of parasitemia ranged from 48% to 57% by time-to-event analysis (one-hazard ratio) (Sirima and Laurens, unpublished; Diawara and Healy, unpublished), and in both Burkina Faso and the most recent Vaccine efficacy (VE) . 90% against homologous (same parasite strain in vaccine and challenge) controlled human malaria infection (CHMI) at 3–11 weeks after last dose has been shown in the United States, Tanzania, and Mali, and can last for at least 14 months. In field studies, during 24 weeks of follow-up post-vaccination in three trials in Mali and one in Burkina Faso, VE against first episode of parasitemia ranged from 48% to 57% by time-to-event analysis (one-hazard ratio) (Sirima and Laurens, unpublished; Diawara and Healy, unpublished), and in both Burkina Faso and the most recent
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