PMID- 32236404
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220224
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 224
IP  - 7
DP  - 2021 Oct 13
TI  - Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and 
      Associated With Protection in a Phase 1/2a Trial.
PG  - 1128-1138
LID - 10.1093/infdis/jiaa144 [doi]
AB  - BACKGROUND: RTS,S is the leading malaria vaccine candidate but only confers 
      partial efficacy against malaria in children. RTS,S is based on the major 
      Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). 
      The induction of anti-CSP antibodies is important for protection; however, it is 
      unclear how these protective antibodies function. METHODS: We quantified the 
      induction of functional anti-CSP antibody responses in healthy malaria-naive 
      adults (N = 45) vaccinated with RTS,S/AS01. This included the ability to mediate 
      effector functions via the fragment crystallizable (Fc) region, such as 
      interacting with human complement proteins and Fcgamma-receptors (FcgammaRs) that are 
      expressed on immune cells, which promote various immunological functions. 
      RESULTS: Our major findings were (1) RTS,S-induced antibodies mediated 
      Fc-dependent effector functions, (2) functional antibodies were generally highest 
      after the second vaccine dose, (3) functional antibodies targeted multiple 
      regions of CSP, (4) participants with higher levels of functional antibodies had 
      a reduced probability of developing parasitemia following homologous challenge 
      (P < .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM. 
      CONCLUSIONS: Our data suggest a role for Fc-dependent antibody effector functions 
      in RTS,S-induced immunity. Enhancing the induction of these functional activities 
      may be a strategy to improve the protective efficacy of RTS,S or other malaria 
      vaccines. CLINICAL TRIALS REGISTRATION: NCT00075049.
CI  - (c) The Author(s) 2020. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Kurtovic, Liriye
AU  - Kurtovic L
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Immunology and Pathology, Monash University, Melbourne, Australia.
FAU - Atre, Tanmaya
AU  - Atre T
AD  - Malaria Vaccine Branch, US Military Malaria Research Program, Walter Reed Army 
      Institute of Research, Silver Spring, Maryland, USA.
FAU - Feng, Gaoqian
AU  - Feng G
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Medicine, University of Melbourne, Parkville, Australia.
FAU - Wines, Bruce D
AU  - Wines BD
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Immunology and Pathology, Monash University, Melbourne, Australia.
AD  - Department of Clinical Pathology, University of Melbourne, Melbourne, Australia.
FAU - Chan, Jo-Anne
AU  - Chan JA
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Immunology and Pathology, Monash University, Melbourne, Australia.
FAU - Boyle, Michelle J
AU  - Boyle MJ
AD  - Burnet Institute, Melbourne, Australia.
AD  - QIMR Berghofer, Herston, Australia.
FAU - Drew, Damien R
AU  - Drew DR
AD  - Burnet Institute, Melbourne, Australia.
FAU - Hogarth, P Mark
AU  - Hogarth PM
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Immunology and Pathology, Monash University, Melbourne, Australia.
AD  - Department of Clinical Pathology, University of Melbourne, Melbourne, Australia.
FAU - Fowkes, Freya J I
AU  - Fowkes FJI
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Epidemiology and Preventative Medicine, Monash University, 
      Melbourne, Australia.
AD  - Department of Infectious Diseases, Monash University, Melbourne, Australia.
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population and 
      Global Health, University of Melbourne, Melbourne, Australia.
FAU - Bergmann-Leitner, Elke S
AU  - Bergmann-Leitner ES
AD  - Malaria Vaccine Branch, US Military Malaria Research Program, Walter Reed Army 
      Institute of Research, Silver Spring, Maryland, USA.
FAU - Beeson, James G
AU  - Beeson JG
AUID- ORCID: 0000-0002-1018-7898
AD  - Burnet Institute, Melbourne, Australia.
AD  - Department of Immunology and Pathology, Monash University, Melbourne, Australia.
AD  - Department of Medicine, University of Melbourne, Parkville, Australia.
AD  - Department of Microbiology, Monash University, Clayton, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT00075049
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Protozoan Proteins)
RN  - 0 (RTS malaria vaccine)
SB  - IM
MH  - Antibodies, Protozoan/*blood
MH  - Antigens, Protozoan
MH  - Humans
MH  - Malaria/blood/*prevention & control
MH  - Malaria Vaccines/*administration & dosage/immunology
MH  - Protozoan Proteins
MH  - *Vaccine Efficacy
PMC - PMC8514181
OTO - NOTNLM
OT  - Plasmodium falciparum
OT  - Fcgamma-receptor
OT  - antibodies
OT  - circumsporozoite protein
OT  - complement
OT  - malaria
OT  - opsonic phagocytosis
OT  - vaccines
EDAT- 2020/04/03 06:00
MHDA- 2022/02/25 06:00
PMCR- 2020/03/31
CRDT- 2020/04/03 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/03/30 00:00 [accepted]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2020/04/03 06:00 [entrez]
PHST- 2020/03/31 00:00 [pmc-release]
AID - 5814271 [pii]
AID - jiaa144 [pii]
AID - 10.1093/infdis/jiaa144 [doi]
PST - ppublish
SO  - J Infect Dis. 2021 Oct 13;224(7):1128-1138. doi: 10.1093/infdis/jiaa144.