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Nat Mater. 2019 Feb;18(2):175-185. doi: 10.1038/s41563-018-0256-5. Epub 2019 Jan 14.

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

Author information

1
Institute for Bioengineering, School of Life Science and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
2
Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA.
3
Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France.
4
Institute for Bioengineering, School of Life Science and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. jhubbell@uchicago.edu.
5
Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.

Abstract

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 αCSP 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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PMID:
30643235
DOI:
10.1038/s41563-018-0256-5
[Indexed for MEDLINE]

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