McIntosh, JD;
Manning, K;
Chokshi, S;
Naoumov, NV;
Fraser, JD;
Dunbar, PR;
Taylor, JA;
(2014)
An engineered non-toxic superantigen increases cross presentation of hepatitis B virus nucleocapsids by human dendritic cells.
PLoS ONE
, 9
(4)
, Article e93598. 10.1371/journal.pone.0093598.
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Abstract
Article Authors Metrics Comments Media Coverage Abstract Introduction Methods Results Discussion Author Contributions References Reader Comments Figures Abstract Virus like particles (VLPs) are potent immunogens capable of priming strong protective antibody responses due to their repetitive structural arrangement and affinity for specific B cell receptors. By contrast, T cell responses to VLPs can be weak due to inefficient uptake and processing by antigen presenting cells. We report here a novel strategy for increasing the T cell reactivity of a VLP, the nucleocapsid of hepatitis B virus, through covalent coupling of M1, an engineered form of the Streptococcal superantigen SMEZ2, that binds MHC II with high affinity but lacks its T cell mitogenic capability. M1:HBcAg conjugates bound to dendritic cells and were efficiently endocytosed into late endosomes. Human dendritic cells pulsed with M1:HBcAgs stimulated HBV-specific CD8+ T cells more effectively than cells pulsed with native capsids indicating that the modified VLP was more effectively cross presented by APCs. Coupling of M1 was also able to induce significantly greater reactivity of human CD4+ T cells specific for a common T-helper epitope. These studies indicate the potential of recombinant superantigens to act as flexible molecular adjuvants that can be incorporated into various subunit vaccine platforms leading to enhanced T cell reactivity in humans.
| Type: | Article |
|---|---|
| Title: | An engineered non-toxic superantigen increases cross presentation of hepatitis B virus nucleocapsids by human dendritic cells |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0093598 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0093598 |
| Language: | English |
| Additional information: | Copyright: © 2014 McIntosh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Copyright: © 2014 McIntosh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203685 |
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