Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia. Issue 31 (17th July 2015)

• Record Type: Journal Article
• Authors: Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A.; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M.
• Is Part Of: Vaccine. Volume 33:Issue 31(2015)
• Page Start: 3746
• Page End: 3751
• Publication Date: 2015-07-17
• Subjects: CYD-TDV dengue vaccine -- PRNT50 antibody titres -- Multivariate regression -- Serotype interactions; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.05.059
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: 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.