Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria

Immunity
Michelle J BoyleJames G Beeson

Abstract

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity.

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Citations

Jan 8, 2016·Parasitology·Freya J I FowkesJames G Beeson
Jan 9, 2016·Parasitology·Danielle I Stanisic, Michael F Good
Jan 9, 2016·Parasitology·Victoria Ryg-CornejoDiana S Hansen
Jan 14, 2016·Expert Review of Vaccines·Kazutoyo Miura
Feb 3, 2016·FEMS Microbiology Reviews·James G BeesonJack S Richards
Jan 19, 2016·Trends in Parasitology·Greta E WeissPaul R Gilson
Jan 5, 2016·Trends in Parasitology·UNKNOWN WAMIN consortium authors include (in alphabetical order):Zenon A Zenonos
Dec 15, 2015·FEMS Microbiology Reviews·Katrien DeroostPhilippe E Van den Steen
Jul 3, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Vashti IraniJames G Beeson
Jun 6, 2016·Current Opinion in Microbiology·Carole A Long, Fidel Zavala
Jul 28, 2016·International Journal for Parasitology·Michelle J BoyleFreya J I Fowkes
Aug 18, 2016·Immunity·Sara L Stone, Frances E Lund
Oct 31, 2016·Trends in Parasitology·Andrew TeoStephen J Rogerson
Sep 8, 2016·Parasitology International·Kyousuke Kobayashi, Kentaro Kato
Nov 2, 2016·Frontiers in Microbiology·Pollyanna S GomesAlexandre Morrot
Jun 25, 2017·Immunology·James TujuFaith H A Osier
Jun 13, 2017·Expert Review of Vaccines·Edward H NtegeTakafumi Tsuboi
Dec 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcela Montes de OcaChristian R Engwerda
Oct 25, 2017·Nature Reviews. Immunology·Lenette L LuGalit Alter
Nov 25, 2016·Clinical and Vaccine Immunology : CVI·Ryan W J SteelStefan H I Kappe
Oct 3, 2018·Biological & Pharmaceutical Bulletin·Yusuke KawaiTakahiko Tamura

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Methods Mentioned

BETA
ELISA
membrane filtration
flow cytometry
column chromatography
ELISAs

Software Mentioned

SE
Stata

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