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  Immunological evaluation of synthetic glycosylphosphatidylinositol glycoconjugates as vaccine candidates against malaria

Malik, A., Steinbeis, F., Carillo, M. A., Seeberger, P. H., Seeberger, P. H., Lepenies, B., et al. (2020). Immunological evaluation of synthetic glycosylphosphatidylinositol glycoconjugates as vaccine candidates against malaria. ACS Chemical Biology, 15(1), 171-178. doi:10.1021/acschembio.9b00739.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-CB0E-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-56CC-4
Genre: Journal Article

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Malik, Ankita1, Author              
Steinbeis, Fridolin, Author
Carillo, Maria Antonietta1, Author              
Seeberger, Peter H., Author              
Seeberger, Peter H.2, Author              
Lepenies, Bernd3, Author              
Varón Silva, Daniel1, Author              
Affiliations:
1Daniel Varón Silva, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863302              
2Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              
3Bernd Lepenies, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863298              

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 Abstract: Glycosylphosphatidylinositols (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 anti-toxic 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 P. 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 (ECM) model using C57BL/6JRj mice. Protection may be dependent on both, the antibody and 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 anti-toxin vaccine candidates against cerebral malaria.

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Language(s): eng - English
 Dates: 2019-10-012020
 Publication Status: Published in print
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 Identifiers: DOI: 10.1021/acschembio.9b00739
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Title: ACS Chemical Biology
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 15 (1) Sequence Number: - Start / End Page: 171 - 178 Identifier: ISSN: 1554-8929