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Immunological Evaluation of Synthetic Glycosylphosphatidylinositol Glycoconjugates as Vaccine Candidates against Malaria
journal contribution
posted on 2019-10-15, 13:36 authored by Ankita Malik, Fridolin Steinbeis, Maria Antonietta Carillo, Peter H. Seeberger, Bernd Lepenies, Daniel Varón SilvaGlycosylphosphatidylinositols
(GPIs) are complex glycolipids present
on the surfaces of Plasmodium parasites that may
act as toxins during the progression of malaria. GPIs can activate
the immune system during infection and induce the formation of anti-GPI
antibodies that neutralize their activity. Therefore, an antitoxic
vaccine based on GPI glycoconjugates may prevent malaria pathogenesis.
To evaluate the role of three key modifications on Plasmodium GPI glycan in the activity of these glycolipids, we synthesized
and investigated six structurally distinct GPI fragments from Plasmodium falciparum. The synthetic glycans were conjugated
to the CRM197 carrier protein and were tested for immunogenicity and
efficacy as antimalarial vaccine candidates in an experimental cerebral
malaria model using C57BL/6JRj mice. Protection may be dependent on
both the antibody and the cellular immune response to GPIs, and the
elicited immune response depends on the orientation of the glycan,
the number of mannoses in the structure, and the presence of the phosphoethanolamine
and inositol units. This study provides insights into the epitopes
in GPIs and contributes to the development of GPI-based antitoxin
vaccine candidates against cerebral malaria.
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anti-GPI antibodiesC 57BL miceGPI glycoconjugatesmalaria pathogenesisSynthetic Glycosylphosphatidylinositol Glycoconjugatesinositol unitsVaccine CandidatesPlasmodium parasitesPlasmodium falciparumantimalarial vaccine candidatesMalaria GlycosylphosphatidylinositolsCRM 197 carrier proteinantitoxic vaccineGPI fragmentsGPI-based antitoxin vaccine candidatesPlasmodium GPI glycanmalaria modelImmunological Evaluation
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