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}
}
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 -
