Imperial College London
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PROFESSOR AJIT LALVANI

Faculty of Medicine, National Heart & Lung Institute

Chair in Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 7594 0883a.lalvani

 
 
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Assistant

 

Dr Luis Berrocal Almanza +44 (0)20 7594 3721

 
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Location

 

Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Masonou:2019:10.1371/journal.pone.0217091,
author = {Masonou, T and Hokey, DA and Lahey, T and Halliday, A and Berrocal-Almanza, LC and Wieland-Alter, WF and Arbeit, RD and Lalvani, A and von, Reyn CF},
doi = {10.1371/journal.pone.0217091},
journal = {PLoS ONE},
title = {CD4+ T cell cytokine responses to the DAR-901 booster vaccine in BCG-primed adults: A randomized, placebo-controlled trial},
url = {http://dx.doi.org/10.1371/journal.pone.0217091},
volume = {14},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: DAR-901 is an inactivated whole cell tuberculosis booster vaccine, prepared using a new scalable, broth-grown method from the master cell bank of SRL172, a vaccine previously shown to prevent tuberculosis. This study examined whether DAR-901 (a) induces CD4+ T cell cytokine profiles previously proposed as correlates of protection and (b) has a specific vaccine-induced immunological signature compared to BCG or placebo. METHODS: We analysed CD4+ T cell cytokine immune responses from 10 DAR-901 recipients, 9 BCG recipients and 9 placebo recipients from the Phase I DAR-901 MDES trial. In that study, HIV-negative, IGRA-negative participants with prior BCG immunization were randomized (double-blind) to receive three intradermal injections of DAR-901 or saline placebo or two injections of saline placebo followed by an intradermal injection of BCG. Antigen-specific functional and phenotypic CD4+ T cell responses along with effector phenotype of responder cells were measured by intracellular cytokine staining. RESULTS: DAR-901 recipients exhibited increased DAR-901 antigen-specific polyfunctional or bifunctional T cell responses compared to baseline. Vaccine specific CD4+ IFNγ, IL2, TNFα and any cytokine responses peaked at 7 days post-dose 3. Th1 responses predominated, with most responder cells exhibiting a polyfunctional effector memory phenotype. BCG induced greater CD4+ T cell responses than placebo while the more modest DAR-901 responses did not differ from placebo. Neither DAR-901 nor BCG induced substantial or sustained Th17 /Th22 cytokine responses. CONCLUSION: DAR-901, a TB booster vaccine grown from the master cell bank of SRL 172 which was shown to prevent TB, induced low magnitude polyfunctional effector memory CD4+ T cell responses. DAR-901 responses were lower than those induced by BCG, a vaccine that has been shown ineffective as a booster to prevent tuberculosis disease. These results suggest that induction of higher levels of CD4+ c
AU  - Masonou,T
AU  - Hokey,DA
AU  - Lahey,T
AU  - Halliday,A
AU  - Berrocal-Almanza,LC
AU  - Wieland-Alter,WF
AU  - Arbeit,RD
AU  - Lalvani,A
AU  - von,Reyn CF
DO  - 10.1371/journal.pone.0217091
PY  - 2019///
SN  - 1932-6203
TI  - CD4+ T cell cytokine responses to the DAR-901 booster vaccine in BCG-primed adults: A randomized, placebo-controlled trial
T2  - PLoS ONE
UR  - http://dx.doi.org/10.1371/journal.pone.0217091
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31120957
UR  - http://hdl.handle.net/10044/1/70427
VL  - 14
ER  -
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