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  4. Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity
 
research article

Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity

Wilson, D. Scott
•
Hirosue, Sachiko  
•
Raczy, Michal M.
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February 1, 2019
Nature Materials

Fully effective vaccines for complex infections must elicit a diverse repertoire of antibodies (humoral immunity) and CD8+ T-cell responses (cellular immunity). Here, we present a synthetic glyco-adjuvant named p(Man-TLR7), which, when conjugated to antigens, elicits robust humoral and cellular immunity. p(Man-TLR7) is a random copolymer composed of monomers that either target dendritic cells (DCs) via mannose-binding receptors or activate DCs via Toll-like receptor 7 (TLR7). Protein antigens are conjugated to p(Man-TLR7) via a self-immolative linkage that releases chemically unmodified antigen after endocytosis, thus amplifying antigen presentation to T cells. Studies with ovalbumin (OVA)-p(Man-TLR7) conjugates demonstrate that OVA-p(Man-TLR7) generates greater humoral and cellular immunity than OVA conjugated to polymers lacking either mannose targeting or TLR7 ligand. We show significant enhancement of Plasmodium falciparum-derived circumsporozoite protein (CSP)-specific T-cell responses, expansion in the breadth of the alpha CSP IgG response and increased inhibition of sporozoite invasion into hepatocytes with CSP-p(Man-TLR7) when compared with CSP formulated with MPLA/QS-21-loaded liposomes-the adjuvant used in the most clinically advanced malaria vaccine. We conclude that our antigen-p(Man-TLR7) platform offers a strategy to enhance the immunogenicity of protein subunit vaccines.

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Type
research article
DOI
10.1038/s41563-018-0256-5
Web of Science ID

WOS:000456325600020

Author(s)
Wilson, D. Scott
Hirosue, Sachiko  
Raczy, Michal M.
Bonilla-Ramirez, Leonardo
Jeanbart, Laura
Wang, Ruyi
Kwissa, Marcin
Franetich, Jean-Francois
Broggi, Maria A. S.
Diaceri, Giacomo
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Date Issued

2019-02-01

Publisher

NATURE PUBLISHING GROUP

Published in
Nature Materials
Volume

18

Issue

2

Start page

175

End page

185

Subjects

Chemistry, Physical

•

Materials Science, Multidisciplinary

•

Physics, Applied

•

Physics, Condensed Matter

•

Chemistry

•

Materials Science

•

Physics

•

dendritic cells

•

t-cells

•

plasmodium-falciparum

•

mannose receptor

•

in-vitro

•

vaccines

•

responses

•

antibody

•

determinant

•

cytokines

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LLCB  
LMRP  
Available on Infoscience
February 6, 2019
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/154373
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