Malik A, Steinbeis F, Carillo MA, Seeberger PH, Lepenies B, Silva DV Immunological Evaluation of Synthetic Glycosylphosphatidylinositol Glycoconjugates as Vaccine Candidates against Malaria ACS Chemical Biology15(1) (2020)
171-178
a-D-Manp-(1-2)-+ /Variants 0/-+ /Variants 1/-+
| | |
Subst-(1-2)-EtN-(1--P--6)--a-D-Manp-(1-2)-a-D-Manp-(1-6)-a-D-Manp-(1-4)-a-D-GlcpN-(1-6)-L-myoIno-(1--P--3)--Gro
|
/Variants 2/-+
/Variants 0/ is:
90%Pam-(1-2)-
OR (exclusively)
10%Myr-(1-2)-
/Variants 1/ is:
88%Ole-(1-2)-
OR (exclusively)
12%Ste-(1-2)-
/Variants 2/ is:
80%Ste-(1-1)-
OR (exclusively)
12%Pam-(1-1)-
Subst = protein
NCBI PubMed ID:31573796 Publication DOI:10.1021/acschembio.9b00739 Journal NLM ID:101282906 Publisher: Washington, DC: American Chemical Society Correspondence: Daniel.Varonmpikg.mpg.de; bernd.lepeniestiho-hannover.de Institutions: Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Arnimallee 22, 14195 Berlin, Germany, Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany, Immunology Unit & Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Bunteweg 17, 30559 Hannover, Germany
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 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.
report error
Found 1 record.
Displayed record 1
, ICD11: XN69B 
mpikg.mpg.de; bernd.lepenies