Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

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.

• Authors: Ilaria Dorigatti, Ricardo Aguas, Christl A Donnelly, Bruno Guy, Laurent Coudeville, Nicholas Jackson, Melanie Saville, Neil M Ferguson
• Journal: Vaccine (Vaccine) Vol. 33 Issue 31 Pg. 3746-51 (Jul 17 2015) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 26051515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antibodies, Viral
• CYD-TDV vaccine
• Dengue Vaccines

Topics

• Adolescent
• Adult
• Antibodies, Viral (blood)
• Asia, Southeastern
• Child
• Child, Preschool
• Clinical Trials, Phase II as Topic
• Dengue Vaccines (administration & dosage, immunology)
• Dengue Virus (immunology)
• Female
• Humans
• Infant
• Latin America
• Male
• Models, Statistical
• Treatment Outcome
• Young Adult