PMID- 31555824
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 71
IP  - 4
DP  - 2020 Aug 14
TI  - 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.
PG  - 1063-1071
LID - 10.1093/cid/ciz925 [doi]
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 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.
CI  - Published by Oxford University Press for the Infectious Diseases Society of 
      America 2019. This work is written by (a) US Government employee(s) and is in the 
      public domain in the US.
FAU - Steinhardt, Laura C
AU  - Steinhardt LC
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
FAU - Richie, Thomas L
AU  - Richie TL
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Yego, Reuben
AU  - Yego R
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Akach, Dorcas
AU  - Akach D
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Hamel, Mary J
AU  - Hamel MJ
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
FAU - Gutman, Julie R
AU  - Gutman JR
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
FAU - Wiegand, Ryan E
AU  - Wiegand RE
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
FAU - Nzuu, Elizabeth L
AU  - Nzuu EL
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Dungani, Allan
AU  - Dungani A
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Kc, Natasha
AU  - Kc N
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Murshedkar, Tooba
AU  - Murshedkar T
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Church, L W Preston
AU  - Church LWP
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Sim, B Kim Lee
AU  - Sim BKL
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Billingsley, Peter F
AU  - Billingsley PF
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - James, Eric R
AU  - James ER
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Abebe, Yonas
AU  - Abebe Y
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Kariuki, Simon
AU  - Kariuki S
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Samuels, Aaron M
AU  - Samuels AM
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
FAU - Otieno, Kephas
AU  - Otieno K
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Sang, Tony
AU  - Sang T
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Kachur, S Patrick
AU  - Kachur SP
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
AD  - Mailman School of Public Health, Columbia University, New York, New York, USA.
FAU - Styers, David
AU  - Styers D
AD  - The Emmes Corporation, Rockville, Maryland, USA.
FAU - Schlessman, Kelly
AU  - Schlessman K
AD  - The Emmes Corporation, Rockville, Maryland, USA.
FAU - Abarbanell, Ginnie
AU  - Abarbanell G
AD  - Washington University School of Medicine and St Louis Children's Hospital, St 
      Louis, Missouri, USA.
FAU - Hoffman, Stephen L
AU  - Hoffman SL
AD  - Sanaria Inc, Rockville, Maryland, USA.
FAU - Seder, Robert A
AU  - Seder RA
AD  - National Institutes of Health, Bethesda, Maryland, USA.
FAU - Oneko, Martina
AU  - Oneko M
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
LA  - eng
SI  - ClinicalTrials.gov/NCT02687373
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Malaria Vaccines)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Child
MH  - Child, Preschool
MH  - Double-Blind Method
MH  - Humans
MH  - Immunogenicity, Vaccine
MH  - Infant
MH  - Kenya
MH  - *Malaria Vaccines/adverse effects
MH  - *Malaria, Falciparum/prevention & control
MH  - Plasmodium falciparum
MH  - Sporozoites
MH  - Vaccination
PMC - PMC7428396
OTO - NOTNLM
OT  - infants
OT  - malaria
OT  - safety
OT  - sporozoite
OT  - vaccine
EDAT- 2019/09/27 06:00
MHDA- 2021/04/28 06:00
PMCR- 2019/09/26
CRDT- 2019/09/27 06:00
PHST- 2019/07/01 00:00 [received]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/09/27 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2019/09/27 06:00 [entrez]
PHST- 2019/09/26 00:00 [pmc-release]
AID - 5573993 [pii]
AID - ciz925 [pii]
AID - 10.1093/cid/ciz925 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2020 Aug 14;71(4):1063-1071. doi: 10.1093/cid/ciz925.