Imperial College London
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Professor Christl Donnelly CBE FMedSci FRS

Faculty of Medicine, School of Public Health

Visiting Professor
 
 
 
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Contact

 

c.donnelly Website

 
 
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Location

 

School of Public HealthWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dorigatti:2015:10.1016/j.vaccine.2015.05.059,
author = {Dorigatti, I and Aguas, R and Donnelly, CA and Guy, B and Coudeville, L and Jackson, N and Saville, M and Ferguson, NM},
doi = {10.1016/j.vaccine.2015.05.059},
journal = {Vaccine},
pages = {3746--3751},
title = {Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.},
url = {http://dx.doi.org/10.1016/j.vaccine.2015.05.059},
volume = {33},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. METHODS: We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. RESULTS: We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. CONCLUSIONS: This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains.
AU  - Dorigatti,I
AU  - Aguas,R
AU  - Donnelly,CA
AU  - Guy,B
AU  - Coudeville,L
AU  - Jackson,N
AU  - Saville,M
AU  - Ferguson,NM
DO  - 10.1016/j.vaccine.2015.05.059
EP  - 3751
PY  - 2015///
SN  - 1873-2518
SP  - 3746
TI  - Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.
T2  - Vaccine
UR  - http://dx.doi.org/10.1016/j.vaccine.2015.05.059
UR  - http://hdl.handle.net/10044/1/24033
VL  - 33
ER  -
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