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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.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.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.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.

Original publication

DOI

10.1016/j.vaccine.2015.05.059

Type

Journal article

Journal

Vaccine

Publication Date

07/2015

Volume

33

Pages

3746 - 3751

Addresses

MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, Norfolk Place, W2 1PG London, United Kingdom. Electronic address: i.dorigatti@imperial.ac.uk.

Keywords

Humans, Dengue Virus, Antibodies, Viral, Treatment Outcome, Models, Statistical, Adolescent, Adult, Child, Child, Preschool, Infant, Latin America, Asia, Southeastern, Female, Male, Dengue Vaccines, Clinical Trials, Phase II as Topic, Young Adult