期刊
VACCINE
卷 33, 期 31, 页码 3746-3751出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.05.059
关键词
CYD-TDV dengue vaccine; PRNT50 antibody titres; Multivariate regression; Serotype interactions
资金
- European Union EMPERIE project
- European Union PREDEMICS project
- National Institute of General Medical Sciences Models of Infectious Disease Agent Study initiative
- Bill and Melinda Gates Foundation [P20064, P46908]
- UK Medical Research Council
- UK National Institute for Health Research
- Medical Research Council [MR/K010174/1, MR/K010174/1B] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10252, NF-SI-0513-10125] Funding Source: researchfish
- MRC [MR/K010174/1] Funding Source: UKRI
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 preexisting 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. (C) 2015 The Authors. Published by Elsevier Ltd.
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