1. Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya
- Author
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Yonas Abebe, Mary J. Hamel, Kephas Otieno, Aaron M. Samuels, Martina Oneko, Laura C. Steinhardt, Simon Kariuki, S. Patrick Kachur, David Styers, Stephen L. Hoffman, Natasha Kc, Allan Dungani, L. W. Preston Church, Eric R. James, Reuben Yego, Tony Sang, Dorcas Akach, Ryan E. Wiegand, Ginnie Abarbanell, B. Kim Lee Sim, Julie Gutman, Elizabeth L Nzuu, Robert A. Seder, Peter F. Billingsley, Thomas L. Richie, Kelly Schlessman, and Tooba Murshedkar
- Subjects
Adult ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Plasmodium falciparum ,030231 tropical medicine ,Placebo ,law.invention ,03 medical and health sciences ,Immunogenicity, Vaccine ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Malaria Vaccines ,Animals ,Humans ,Medicine ,Malaria, Falciparum ,Child ,Adverse effect ,Articles and Commentaries ,business.industry ,Vaccination ,Infant ,medicine.disease ,Kenya ,PfSPZ vaccine ,Circumsporozoite protein ,Clinical trial ,030104 developmental biology ,Infectious Diseases ,Sporozoites ,Child, Preschool ,business ,Malaria - Abstract
Background The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited. Methods We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5–9 years, 13–59 months, and 5–12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay. Results Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. No related grade 3 AEs, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P < .001). Conclusions PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic. Clinical Trials Registration NCT02687373.
- Published
- 2019