Multi-Dose Priming Regimens of PfSPZ Vaccine: Safety and Efficacy against Controlled Human Malaria Infection in Equatoguinean Adults
Author:
Jongo Said Abdallah1, Church L. W. Preston2, Nchama Vicente Urbano Nsue Ndong3, Hamad Ali1, Chuquiyauri Raul2, Kassim Kamaka Ramadhani1, Athuman Thabit1, Deal Anna45, Natasha KC26, Mtoro Ali1, Mpina Maxmillian45, Nyakarungu Elizabeth1, Bidjimi Gertrudis Owono3, Owono Marta Alene3, Mayé Escolástica Raquel Mansogo3, Mangue Martín Eká Ondó3, Okomo Genaro Nsué Nguema3, Pasialo Beltrán Ekuá Ntutumu3, Mandumbi Dolores Mbang Ondó3, Mikue María-Silvia A. López3, Mochomuemue Fortunata Lobede3, Obono Mariano Obiang3, Besahá Juan Carlos Momo3, Bijeri José Raso3, Abegue Gabriel Mbá3, Veri Yolanda Rimoy3, Bela Ines Toichoa3, Chochi Federico Comsil3, Lima Sánchez José Enrique3, Pencelli Vanessa2, Gayozo Griselda3, Nlang José Antonio Esono Mbá3, Schindler Tobias45, James Eric R.2, Abebe Yonas2, Lemiale Laurence2, Stabler Thomas C.2, Murshedkar Tooba2, Chen Mei-Chun2, Schwabe Christopher7, Ratsirarson Josea7, Rivas Matilde Riloha3, Ayekaba Mitoha Ondo’o3, Milang Diosdado Vicente Nsué3, Falla Carlos Cortés7, Phiri Wonder P.7, García Guillermo A.7, Maas Carl D.8, Nlavo Bonifacio Manguire8, Tanner Marcel45, Billingsley Peter F.2, Kim Lee Sim B.26, Daubenberger Claudia45, Hoffman Stephen L.2, Abdulla Salim1, Richie Thomas L.2
Affiliation:
1. 1Bagamoyo Research and Training Center, Ifakara Health Institute, Bagamoyo, Tanzania; 2. 2Sanaria Inc., Rockville, Maryland; 3. 3Ministry of Health and Social Welfare, Equatorial Guinea, Malabo, Equatorial Guinea; 4. 4Clinical Immunology Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; 5. 5University of Basel, Basel, Switzerland; 6. 6Protein Potential LLC, Rockville, Maryland; 7. 7Medical Care Development International (MCDI), Silver Spring, Maryland; 8. 8Marathon EG Production, Ltd., Bioko Norte, Equatorial Guinea
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.
Publisher
American Society of Tropical Medicine and Hygiene
Subject
Virology,Infectious Diseases,Parasitology
Cited by
18 articles.
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