Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure

BMC Medicine
Liriye KurtovicJames G Beeson

Abstract

Leading malaria vaccine, RTS,S, is based on the circumsporozoite protein (CSP) of sporozoites. RTS,S confers partial protection against malaria in children, but efficacy wanes relatively quickly after primary immunization. Vaccine efficacy has some association with anti-CSP IgG; however, it is unclear how these antibodies function, and how functional antibodies are induced and maintained over time. Recent studies identified antibody-complement interactions as a potentially important immune mechanism against sporozoites. Here, we investigated whether RTS,S vaccine-induced antibodies could function by interacting with complement. Serum samples were selected from children in a phase IIb trial of RTS,S/AS02A conducted at two study sites of high and low malaria transmission intensity in Manhiça, Mozambique. Samples following primary immunization and 5-year post-immunization follow-up time points were included. Vaccine-induced antibodies were characterized by isotype, subclass, and epitope specificity, and tested for the ability to fix and activate complement. We additionally developed statistical methods to model the decay and determinants of functional antibodies after vaccination. RTS,S vaccination induced anti-CSP antibodies that...Continue Reading

References

Mar 1, 1989·Transactions of the Royal Society of Tropical Medicine and Hygiene·A E BrownJ B Gingrich
Feb 15, 2001·The Journal of Infectious Diseases·K E KesterUNKNOWN RTS,S Malaria Vaccine Evaluation Group
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica L TeelingJan G J van de Winkel
Dec 10, 2008·The New England Journal of Medicine·Philip BejonLorenz von Seidlein
Jul 28, 2009·The Journal of Biological Chemistry·Matthew L PlassmeyerDavid L Narum
Jun 18, 2010·Vaccine·Sofia CasaresThomas L Richie
Apr 24, 2012·Current Opinion in Immunology·Carl R AlvingSteven G Reed
Nov 19, 2013·Lancet·Vasee S MoorthyJean-Marie Okwo-Bele
Dec 3, 2013·The Journal of Clinical Investigation·Lander FoquetGeert Leroux-Roels
Mar 15, 2014·Science·Christoph A DiebolderPaul W H I Parren

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Citations

Sep 24, 2019·Human Vaccines & Immunotherapeutics·Matthew B Laurens
Sep 27, 2019·Immunological Reviews·Liriye KurtovicJames G Beeson
Jun 12, 2020·Immunological Investigations·Cecilia NapodanoUmberto Basile
Sep 28, 2020·Parasite Immunology·Kelvin Mokaya AbugaJulius Clemence R Hafalla
Nov 6, 2020·Immunology and Cell Biology·Liriye KurtovicJames G Beeson
Jan 28, 2021·Expert Review of Vaccines·Danielle I Stanisic, Matthew B B McCall
Feb 16, 2021·Frontiers in Immunology·Isaac SsewanyanaKevin K A Tetteh
Apr 3, 2021·International Journal for Parasitology·Sakineh PirahmadiAkram A Mehrizi
Apr 28, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Leah MaharajMoses Okpeku
Jul 3, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Ali AsghariFattaneh Montazeri
Jun 26, 2021·Frontiers in Immunology·Dilini RathnayakeStephen J Rogerson
Aug 10, 2021·Current Epidemiology Reports·Griffin J BellJeffrey A Bailey
Sep 18, 2021·Expert Review of Vaccines·D Herbert OpiJames G Beeson
Nov 4, 2021·Parasitology International·Yanie TayiptoRhea J Longley
Dec 4, 2021·Malaria Journal·Robert M MugoFrancis M Ndungu

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA

Clinical Trials Mentioned

NCT00197041

Software Mentioned

GraphPad Prism
Stata

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