Imperial College London
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ProfessorJonathanWeber

Faculty of Medicine, Department of Infectious Disease

Director of the AHSC, Professor of Communicable Diseases
 
 
 
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Contact

 

+44 (0)20 7594 3905j.weber

 
 
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Assistant

 

Mrs Siobhan Pigott +44 (0)20 7594 3901

 
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Location

 

2.15Faculty BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Knudsen:2015:10.1371/journal.pone.0117042,
author = {Knudsen, ML and Ljungberg, K and Tatoud, R and Weber, J and Esteban, M and Liljestrom, P},
doi = {10.1371/journal.pone.0117042},
journal = {PLOS One},
title = {Alphavirus Replicon DNA Expressing HIV Antigens Is an Excellent Prime for Boosting with Recombinant Modified Vaccinia Ankara (MVA) or with HIV gp140 Protein Antigen},
url = {http://dx.doi.org/10.1371/journal.pone.0117042},
volume = {10},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Vaccination with DNA is an attractive strategy for induction of pathogen-specific T cells andantibodies. Studies in humans have shown that DNA vaccines are safe, but their immuno-genicity needs further improvement. As a step towards this goal, we have previously dem-onstrated that immunogenicity is increased with the use of an alphavirus DNA-launchedreplicon (DREP) vector compared to conventional DNA vaccines. In this study, we investi-gated the effect of varying the dose and number of administrations of DREP when given asa prime prior to a heterologous boost with poxvirus vector (MVA) and/or HIV gp140 proteinformulated in glucopyranosyl lipid A (GLA-AF) adjuvant. The DREP and MVA vaccine con-structs encoded Env and a Gag-Pol-Nef fusion protein from HIV clade C. One to three ad-ministrations of 0.2μg DREP induced lower HIV-specific T cell and IgG responses than theequivalent number of immunizations with 10μg DREP. However, the two doses were equal-ly efficient as a priming component in a heterologous prime-boost regimen. The magnitudeof immune responses depended on the number of priming immunizations rather than thedose. A single low dose of DREP prior to a heterologous boost resulted in greatly increasedimmune responses compared to MVA or protein antigen alone, demonstrating that a mere0.2μg DREP was sufficient for priming immune responses. Following a DREP prime, T cellresponses were expanded greatly by an MVA boost, and IgG responses were also expand-ed when boosted with protein antigen. When MVA and protein were administered simulta-neously following multiple DREP primes, responses were slightly compromised comparedto administering them sequentially. In conclusion, we have demonstrated efficient primingof HIV-specific T cell and IgG responses with a low dose of DREP, and shown that the prim-ing effect depends on number of primes administered rather than dose.
AU  - Knudsen,ML
AU  - Ljungberg,K
AU  - Tatoud,R
AU  - Weber,J
AU  - Esteban,M
AU  - Liljestrom,P
DO  - 10.1371/journal.pone.0117042
PY  - 2015///
SN  - 1932-6203
TI  - Alphavirus Replicon DNA Expressing HIV Antigens Is an Excellent Prime for Boosting with Recombinant Modified Vaccinia Ankara (MVA) or with HIV gp140 Protein Antigen
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0117042
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348821200032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/50812
VL  - 10
ER  -
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