Multi-Dose Priming Regimens of PfSPZ Vaccine: Safety and Efficacy against Controlled Human Malaria Infection in Equatoguinean Adults
Authors: Jongo Said Abdallah , Church L. W. Preston , Nchama Vicente Urbano Nsue Ndong , Hamad Ali , Chuquiyauri Raul , Kassim Kamaka Ramadhani , Athuman Thabit , Deal Anna , Natasha KC , Mtoro Ali , Mpina Maxmillian , Nyakarungu Elizabeth , Bidjimi Gertrudis Owono , Owono Marta Alene , Mayé Escolástica Raquel Mansogo , Mangue Martín Eká Ondó , Okomo Genaro Nsué Nguema , Pasialo Beltrán Ekuá Ntutumu , Mandumbi Dolores Mbang Ondó , Mikue María-Silvia A. López , Mochomuemue Fortunata Lobede , Obono Mariano Obiang , Besahá Juan Carlos Momo , Bijeri José Raso , Abegue Gabriel Mbá , Veri Yolanda Rimoy , Bela Ines Toichoa , Chochi Federico Comsil , Lima Sánchez José Enrique , Pencelli Vanessa , Gayozo Griselda , Nlang José Antonio Esono Mbá , Schindler Tobias , James Eric R. , Abebe Yonas , Lemiale Laurence , Stabler Thomas C. , Murshedkar Tooba , Chen Mei-Chun , Schwabe Christopher , Ratsirarson Josea , Rivas Matilde Riloha , Ayekaba Mitoha Ondo’o , Milang Diosdado Vicente Nsué , Falla Carlos Cortés , Phiri Wonder P. , García Guillermo A. , Maas Carl D. , Nlavo Bonifacio Manguire , Tanner Marcel , Billingsley Peter F. , Kim Lee Sim B. , Daubenberger Claudia , Hoffman Stephen L. , Abdulla Salim , Richie Thomas L. 
Published: February 2022

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.