PMID- 34518679
OWN - NLM
STAT- MEDLINE
DCOM- 20211008
LR  - 20220608
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 27
IP  - 9
DP  - 2021 Sep
TI  - Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants 
      in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial.
PG  - 1636-1645
LID - 10.1038/s41591-021-01470-y [doi]
AB  - The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine 
      provides protection against P. falciparum infection in malaria-naive adults. 
      Preclinical studies show that T cell-mediated immunity is required for protection 
      and is readily induced in humans after vaccination. However, previous malaria 
      exposure can limit immune responses and vaccine efficacy (VE) in adults. We 
      hypothesized that infants with less previous exposure to malaria would have 
      improved immunity and protection. We conducted a multi-arm, randomized, 
      double-blind, placebo-controlled trial in 336 infants aged 5-12 months to 
      determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ 
      Vaccine in infants in a high-transmission malaria setting in western Kenya ( 
      NCT02687373 ). Groups of 84 infants each received 4.5 x 10(5), 9.0 x 10(5) or 
      1.8 x 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine 
      was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in 
      the placebo group experienced related solicited adverse events (AEs) within 28 d 
      postvaccination and most were mild. There was 1 grade 3-related solicited AE in 
      the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more 
      common in the highest-dose group (14.3%) compared to 6.0% of controls, with most 
      being attributed to malaria. There was no significant protection against P. 
      falciparum infection in any dose group at 6 months (VE in the 9.0 x 10(5) dose 
      group = -6.5%, P = 0.598, the primary statistical end point of the study). VE 
      against clinical malaria 3 months after the last dose in the highest-dose group 
      was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent 
      increase in antibody responses that correlated with VE at 6 months in the lowest- 
      and highest-dose groups. T cell responses were undetectable across all dose 
      groups. Detection of Vdelta2(+)Vgamma9(+) T cells, which have been correlated with 
      induction of PfSPZ Vaccine T cell immunity and protection in adults, were 
      infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is 
      age-dependent and may be influenced by Vdelta2(+)Vgamma9(+) T cell frequency. Since there 
      was no significant VE at 6 months in these infants, these vaccine regimens will 
      likely not be pursued further in this age group.
CI  - (c) 2021. This is a U.S. government work and not under copyright protection in the 
      U.S.; foreign copyright protection may apply.
FAU - Oneko, Martina
AU  - Oneko M
AUID- ORCID: 0000-0003-0021-3324
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya. tinaoneko@gmail.com.
FAU - Steinhardt, Laura C
AU  - Steinhardt LC
AUID- ORCID: 0000-0003-0540-9940
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
FAU - Yego, Reuben
AU  - Yego R
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Wiegand, Ryan E
AU  - Wiegand RE
AUID- ORCID: 0000-0002-9486-1850
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
FAU - Swanson, Phillip A
AU  - Swanson PA
AD  - Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
FAU - Kc, Natasha
AU  - Kc N
AD  - Sanaria, Rockville, MD, USA.
FAU - Akach, Dorcas
AU  - Akach D
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 - Gutman, Julie R
AU  - Gutman JR
AUID- ORCID: 0000-0001-6769-7322
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, GA, 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 - Kim Lee Sim, B
AU  - Kim Lee Sim B
FAU - Oloo, Paul Ndaya
AU  - Oloo PN
AUID- ORCID: 0000-0002-9771-5525
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Otieno, Kephas
AU  - Otieno K
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Bii, Dennis K
AU  - Bii DK
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Billingsley, Peter F
AU  - Billingsley PF
AUID- ORCID: 0000-0003-1142-4813
AD  - Sanaria, Rockville, MD, USA.
FAU - James, Eric R
AU  - James ER
AD  - Sanaria, Rockville, MD, 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
AUID- ORCID: 0000-0002-8355-8186
AD  - Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global 
      Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
AD  - Division of Parasitic Diseases and Malaria, Centers for Disease Control and 
      Prevention, Kisumu, Kenya.
FAU - Jongo, Said
AU  - Jongo S
AD  - Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, 
      Tanzania.
FAU - Chebore, Winnie
AU  - Chebore W
AD  - Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, 
      Kenya.
FAU - Abdulla, Salim
AU  - Abdulla S
AD  - Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, 
      Tanzania.
FAU - Daubenberger, Claudia
AU  - Daubenberger C
AD  - Swiss Tropical and Public Health Institute, Basel, Switzerland.
AD  - University of Basel, Basel, Switzerland.
FAU - Mpina, Maxmillian
AU  - Mpina M
AD  - Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, 
      Tanzania.
FAU - Styers, David
AU  - Styers D
AD  - The Emmes Corporation, Rockville, MD, USA.
FAU - Potter, Gail E
AU  - Potter GE
AD  - The Emmes Corporation, Rockville, MD, USA.
FAU - Abarbanell, Ginnie
AU  - Abarbanell G
AD  - Washington University School of Medicine and St Louis Children's Hospital, St 
      Louis, MO, USA.
FAU - Richie, Thomas L
AU  - Richie TL
AUID- ORCID: 0000-0002-2946-5456
AD  - Sanaria, Rockville, MD, USA.
FAU - Hoffman, Stephen L
AU  - Hoffman SL
AUID- ORCID: 0000-0002-0700-9505
AD  - Sanaria, Rockville, MD, USA.
FAU - Seder, Robert A
AU  - Seder RA
AUID- ORCID: 0000-0003-3133-0849
AD  - Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA. 
      rseder@mail.nih.gov.
LA  - eng
SI  - ClinicalTrials.gov/NCT02687373
GR  - R44 AI055229/AI/NIAID NIH HHS/United States
GR  - R44 AI058375/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20210913
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Malaria Vaccines)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
CIN - Nat Microbiol. 2021 Nov;6(11):1345-1346. PMID: 34635830
CIN - Med. 2021 Dec 10;2(12):1289-1291. PMID: 35590146
MH  - Adult
MH  - Antibody Formation/drug effects/immunology
MH  - B-Lymphocytes/drug effects/immunology
MH  - Double-Blind Method
MH  - Humans
MH  - Infant
MH  - Kenya/epidemiology
MH  - Malaria Vaccines/*administration & dosage/adverse effects
MH  - Malaria, Falciparum/*drug therapy/immunology/parasitology/prevention & control
MH  - Plasmodium falciparum/*drug effects/pathogenicity
MH  - Sporozoites/drug effects/pathogenicity
MH  - T-Lymphocytes/drug effects
MH  - Vaccination
MH  - Vaccines, Attenuated/*administration & dosage/adverse effects
EDAT- 2021/09/15 06:00
MHDA- 2021/10/09 06:00
CRDT- 2021/09/14 06:45
PHST- 2021/03/16 00:00 [received]
PHST- 2021/07/16 00:00 [accepted]
PHST- 2021/09/15 06:00 [pubmed]
PHST- 2021/10/09 06:00 [medline]
PHST- 2021/09/14 06:45 [entrez]
AID - 10.1038/s41591-021-01470-y [pii]
AID - 10.1038/s41591-021-01470-y [doi]
PST - ppublish
SO  - Nat Med. 2021 Sep;27(9):1636-1645. doi: 10.1038/s41591-021-01470-y. Epub 2021 Sep 
      13.