TY - JOUR
T1 - Safety, tolerability, and immunogenicity of plasmodium falciparum sporozoite vaccine administered by direct venous inoculation to infants and young children
T2 - Findings from an age de-escalation, dose-escalation, double-blind, randomized controlled study in Western Kenya
AU - Steinhardt, Laura C.
AU - Richie, Thomas L.
AU - Yego, Reuben
AU - Akach, Dorcas
AU - Hamel, Mary J.
AU - Gutman, Julie R.
AU - Wiegand, Ryan E.
AU - Nzuu, Elizabeth L.
AU - Dungani, Allan
AU - KC, Natasha
AU - Murshedkar, Tooba
AU - Preston Church, L. W.
AU - Kim Lee Sim, B.
AU - Billingsley, Peter F.
AU - James, Eric R.
AU - Abebe, Yonas
AU - Kariuki, Simon
AU - Samuels, Aaron M.
AU - Otieno, Kephas
AU - Sang, Tony
AU - Patrick Kachur, S.
AU - Styers, David
AU - Schlessman, Kelly
AU - Abarbanell, Ginnie
AU - Hoffman, Stephen L.
AU - Seder, Robert A.
AU - Oneko, Martina
N1 - Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - 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.
AB - 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.
KW - Infants
KW - Malaria
KW - Safety
KW - Sporozoite
KW - Vaccine
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U2 - 10.1093/cid/ciz925
DO - 10.1093/cid/ciz925
M3 - Article
C2 - 31555824
AN - SCOPUS:85089609857
SN - 1058-4838
VL - 71
SP - 1063
EP - 1071
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -