Imperial College London
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DrSarahJoseph

Faculty of Medicine, Department of Infectious Disease

Clinical Immunologist
 
 
 
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Contact

 

s.joseph

 
 
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Location

 

457Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{McKay:2014:10.1371/journal.pone.0084707,
author = {McKay, PF and Cope, AV and Mann, JFS and Joseph, S and Esteban, M and Tatoud, R and Carter, D and Reed, SG and Weber, J and Shattock, RJ},
doi = {10.1371/journal.pone.0084707},
journal = {PLOS One},
title = {Glucopyranosyl lipid A adjuvant significantly enhances HIV specific T and B cell responses elicited by a DNA-MVA-protein vaccine regimen},
url = {http://dx.doi.org/10.1371/journal.pone.0084707},
volume = {9},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Using a unique vaccine antigen matched and single HIV Clade C approach we have assessed the immunogenicity of a DNApoxvirus-proteinstrategy in mice and rabbits, administering MVA and protein immunizations either sequentially orsimultaneously and in the presence of a novel TLR4 adjuvant, GLA-AF. Mice were vaccinated with combinations of HIV env/gag-pol-nef plasmid DNA followed by MVA-C (HIV env/gag-pol-nef) with HIV CN54gp140 protein (+/2GLA-AF adjuvant) andeither co-administered in different muscles of the same animal with MVA-C or given sequentially at 3-week intervals. TheDNA prime established a population of B cells that were able to mount a statistically significant anamnestic response to theboost vaccines. The greatest antigen-specific antibody response was observed in animals that received all vaccinecomponents. Moreover, a high proportion of the total mucosal IgG (20 – 50%) present in the vaginal vault of thesevaccinated animals was vaccine antigen-specific. The potent elicitation of antigen-specific immune responses to this vaccinemodality was also confirmed in rabbits. Importantly, co-administration of MVA-C with the GLA-AF adjuvanted HIVCN54gp140 protein significantly augmented the antigen-specific T cell responses to the Gag antigen, a transgene productexpressed by the MVA-C vector in a separate quadriceps muscle. We have demonstrated that co-administration of MVA andGLA-AF adjuvanted HIV CN54gp140 protein was equally effective in the generation of humoral responses as a sequentialvaccination modality thus shortening and simplifying the immunization schedule. In addition, a significant further benefit ofthe condensed vaccination regime was that T cell responses to proteins expressed by the MVA-C were potently enhanced,an effect that was likely due to enhanced immunostimulation in the presence of systemic GLA-AF.
AU  - McKay,PF
AU  - Cope,AV
AU  - Mann,JFS
AU  - Joseph,S
AU  - Esteban,M
AU  - Tatoud,R
AU  - Carter,D
AU  - Reed,SG
AU  - Weber,J
AU  - Shattock,RJ
DO  - 10.1371/journal.pone.0084707
PY  - 2014///
SN  - 1932-6203
TI  - Glucopyranosyl lipid A adjuvant significantly enhances HIV specific T and B cell responses elicited by a DNA-MVA-protein vaccine regimen
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0084707
UR  - http://hdl.handle.net/10044/1/31321
VL  - 9
ER  -
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