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
09/2019
Journal Article
Authors:
Steinhardt, L. C.;
Richie, T. L.;
Yego, R.;
Akach, D.;
Hamel, M. J.;
Gutman, J. R.;
Wiegand, R. E.;
Nzuu, E. L.;
Dungani, A.;
Kc, N.;
Murshedkar, T.;
Church, L. W. P.;
Sim, B. K. L.;
Billingsley, P. F.;
James, E. R.;
Abebe, Y.;
Kariuki, S.;
Samuels, A. M.;
Otieno, K.;
Sang, T.;
Kachur, S. P.;
Styers, D.;
Schlessman, K. ;
Abarbanell, G.;
Hoffman, S. L.;
Seder, R. A.;
Oneko, M.
Volume:
71
Pagination:
1063-1071
Issue:
4
Journal:
Clin Infect Dis
PMID:
31555824
URL:
https://www.ncbi.nlm.nih.gov/pubmed/31555824
Keywords:
Adult Animals Child Child, Preschool Double-Blind Method Humans Immunogenicity, Vaccine Infant Kenya *Malaria Vaccines/adverse effects *Malaria, Falciparum/prevention & control Plasmodium falciparum Sporozoites Vaccination infants malaria safety
sporozoite vaccine
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 x 105, 2.7 x 105, 4.5 x 105, 9.0 x 105, and 1.8 x 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 x 105 and 1.8 x 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 x 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic. CLINICAL TRIALS REGISTRATION: NCT02687373.
