Imperial College London
Alternate

ProfessorStellaKnight

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 8869 3494s.knight Website

 
 
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Assistant

 

Ms Alison Scoggins +44 (0)20 8869 3534

 
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Location

 

7W032Northwick ParkNorthwick Park and St Marks Site

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Summary

 

Publications

Citation

BibTex format

@article{Reddi:2021:10.3390/vaccines9080929,
author = {Reddi, D and Durant, L and Bernardo, D and Noble, A and English, NR and Hendy, P and Clark, GC and Prior, JL and Williamson, ED and Knight, SC},
doi = {10.3390/vaccines9080929},
journal = {Vaccines},
pages = {1--10},
title = {In vitro priming of human T cells by dendritic cells provides a screening tool for candidate vaccines for Burkholderia pseudomallei},
url = {http://dx.doi.org/10.3390/vaccines9080929},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei, by co-culture with syngeneic B. pseudomallei-pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1β. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4+ fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei, the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei, fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei. Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimula
AU  - Reddi,D
AU  - Durant,L
AU  - Bernardo,D
AU  - Noble,A
AU  - English,NR
AU  - Hendy,P
AU  - Clark,GC
AU  - Prior,JL
AU  - Williamson,ED
AU  - Knight,SC
DO  - 10.3390/vaccines9080929
EP  - 10
PY  - 2021///
SN  - 2076-393X
SP  - 1
TI  - In vitro priming of human T cells by dendritic cells provides a screening tool for candidate vaccines for Burkholderia pseudomallei
T2  - Vaccines
UR  - http://dx.doi.org/10.3390/vaccines9080929
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000689949500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.mdpi.com/2076-393X/9/8/929
UR  - http://hdl.handle.net/10044/1/91616
VL  - 9
ER  -
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