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Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate.

Authors :
Broecker, Felix
Götze, Sebastian
Hudon, Jonathan
Rathwell, Dominea C. K.
Pereira, Claney L.
Stallforth, Pierre
Anish, Chakkumkal
Seeberger, Peter H.
Source :
Journal of Medicinal Chemistry. 6/14/2018, Vol. 61 Issue 11, p4918-4927. 10p.
Publication Year :
2018

Abstract

Fully synthetic glycan-based vaccines hold great potential as preventive and therapeutic vaccines against infectious diseases as well as cancer. Here, we present a two-component platform based on the facile conjugation of carbohydrate antigens to α-galactosylceramide (a-GalCer) to yield fully synthetic vaccine candidates. Formulation of the cancer-associated Tn antigen glycolipid model vaccine candidate into liposomes of different sizes and subsequent immunization of mice generated specific, high-affinity antibodies against the carbohydrate antigen with characteristics of T cell-dependent immunity. Liposome formulation elicited more reproducible glycan immunity than a conventional glycoconjugate vaccine bearing the same glycan antigen did. Further evaluation of the immune response revealed that the size of the liposomes influenced the glycan antibody responses toward either a cellular (Th1) or a humoral (Th2) immune phenotype. The glycolipid vaccine platform affords strong and robust antiglycan antibody responses in vivo without the need for an external adjuvant. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00222623
Volume :
61
Issue :
11
Database :
Academic Search Index
Journal :
Journal of Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
130291253
Full Text :
https://doi.org/10.1021/acs.jmedchem.8b00312