The currently best estimate for worldwide dengue vaccine efficacy

2016 ◽  
Author(s):  
Maíra Aguiar ◽  
Luís Mateus ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Dengue Vaccine ◽  
Best Estimate

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 674
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals Neutralizing Antibody Correlates Analysis of Tetravalent Dengue Vaccine Efficacy Trials in Asia and Latin America

2017 ◽  
Vol 217 (5) ◽  
pp. 742-753 ◽  
Author(s):  
Zoe Moodie ◽  
Michal Juraska ◽  
Ying Huang ◽  
Yingying Zhuang ◽  
Youyi Fong ◽  
...  
Keyword(s):  
Latin America ◽  
Vaccine Efficacy ◽  
Neutralizing Antibody ◽  
Dengue Vaccine ◽  
Efficacy Trials

scholarly journals An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections

2016 ◽  
Author(s):  
T. Alex Perkins ◽  
Robert C. Reiner ◽  
Guido España ◽  
Quirine A. ten Bosch ◽  
Amit Verma ◽  
...  
Keyword(s):  
Public Health ◽  
Dengue Virus ◽  
Vaccine Efficacy ◽  
Denv Infection ◽  
Health Impact ◽  
Public Health Impact ◽  
Statistical Uncertainty ◽  
Dengue Vaccine ◽  
Agent Based ◽  
Biological Uncertainty

ABSTRACTGiven the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia® from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) “statistical uncertainty” about the numerical value of the vaccine’s efficacy against disease, and (2) “biological uncertainty” about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia® took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccine’s public health impact.

scholarly journals Dependency of Vaccine Efficacy on Preexposure and Age: A Closer Look at a Tetravalent Dengue Vaccine

2017 ◽  
Vol 66 (2) ◽  
pp. 178-184 ◽  
Author(s):  
Yang Yang ◽  
Ya Meng ◽  
M Elizabeth Halloran ◽  
Ira M Longini
Keyword(s):  
Vaccine Efficacy ◽  
Dengue Vaccine

scholarly journals Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against DENV-2 and -4

2018 ◽  
Vol 92 (12) ◽  
pp. e00440-18 ◽  
Author(s):  
Veronique Barban ◽  
Nathalie Mantel ◽  
Aymeric De Montfort ◽  
Anke Pagnon ◽  
Fabrine Pradezynski ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Clinical Efficacy ◽  
Nonhuman Primate ◽  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Denv Infection ◽  
Dengue Vaccine ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Translational Approach

ABSTRACTRecent data obtained with the live-attenuated tetravalent dengue CYD-TDV vaccine showed higher protective efficacy against dengue virus type 4 (DENV-4) than against DENV-2. In contrast, results from previous studies in nonhuman primates predicted comparable high levels of protection against each serotype. Maximum viral loads achieved in macaques by subcutaneous inoculation of DENV are generally much lower than those observed in naturally dengue virus-infected humans. This may contribute to an overestimation of vaccine efficacy. Using more-stringent DENV infection conditions consisting of the intravenous inoculation of 10750% cell culture infectious doses (CCID50) in CYD-TDV-vaccinated macaques, complete protection (i.e., undetectable viral RNA) was achieved in all 6 monkeys challenged with DENV-4 and in 6/18 of those challenged with DENV-2, including transiently positive animals. All other infected macaques (12/18) developed sustained DENV-2 RNAemia (defined as detection of viral RNA in serum samples) although 1 to 3 log10units below the levels achieved in control animals. Similar results were obtained with macaques immunized with either CYD-TDV or monovalent (MV) CYD-2. This suggests that partial protection against DENV-2 was mediated mainly by CYD-2 and not by the other CYDs. Postchallenge induction of strong anamnestic responses, suggesting efficient vaccine priming, likely contributed to the reduction of DENV-2 RNAemia. Finally, an inverse correlation between DENV RNA titers postchallenge and vaccine-induced homotypic neutralizing antibody titers prechallenge was found, emphasizing the key role of these antibodies in controlling DENV infection. Collectively, these data show better agreement with reported data on CYD-TDV clinical vaccine efficacy against DENV-2 and DENV-4. Despite inherent limitations of the nonhuman primate model, these results reinforce its value in assessing the efficacy of dengue vaccines.IMPORTANCEThe nonhuman primate (NHP) model is the most widely recognized tool for assessing the protective activity of dengue vaccine candidates, based on the prevention of postinfection DENV viremia. However, its use has been questioned after the recent CYD vaccine phase III trials, in which moderate protective efficacy against DENV-2 was reported, despite full protection against DENV-2 viremia previously being demonstrated in CYD-vaccinated monkeys. Using a reverse translational approach, we show here that the NHP model can be improved to achieve DENV-2 protection levels that show better agreement with clinical efficacy. With this new model, we demonstrate that the injection of the CYD-2 component of the vaccine, in either a monovalent or a tetravalent formulation, is able to reduce DENV-2 viremia in all immunized animals, and we provide clear statistical evidence that DENV-2-neutralizing antibodies are able to reduce viremia in a dose-dependent manner.

scholarly journals Dengue Vaccine Efficacy: A Systematic Review

2018 ◽  
Vol 21 ◽  
pp. S148-S149
Author(s):  
M Santos ◽  
BR Tura ◽  
LT Silveira
Keyword(s):  
Systematic Review ◽  
Vaccine Efficacy ◽  
Dengue Vaccine

scholarly journals Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America

2018 ◽  
Vol 24 (7) ◽  
pp. 755-763 ◽  
Author(s):  
J.L. Arredondo-García ◽  
S.R. Hadinegoro ◽  
H. Reynales ◽  
M.N. Chua ◽  
D.M. Rivera Medina ◽  
...  
Keyword(s):  
Latin America ◽  
Randomized Controlled Trials ◽  
Vaccine Efficacy ◽  
Controlled Trials ◽  
Dengue Vaccine ◽  
Randomized Controlled

Dengue vaccine efficacy trial: does interference cause failure?

2013 ◽  
Vol 13 (3) ◽  
pp. 191-192 ◽  
Author(s):  
Sathyamangalam Swaminathan ◽  
Navin Khanna ◽  
Belinda Herring ◽  
Suresh Mahalingam
Keyword(s):  
Vaccine Efficacy ◽  
Efficacy Trial ◽  
Dengue Vaccine

Detection of dengue cases by serological testing in a dengue vaccine efficacy trial: Utility for efficacy evaluation and impact of future vaccine introduction

Vaccine ◽  
2016 ◽  
Vol 34 (24) ◽  
pp. 2707-2712 ◽  
Author(s):  
Eric Plennevaux ◽  
Arunee Sabchareon ◽  
Kriengsak Limkittikul ◽  
Pornthep Chanthavanich ◽  
Chukiat Sirivichayakul ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Serological Testing ◽  
Efficacy Trial ◽  
Dengue Vaccine ◽  
Efficacy Evaluation ◽  
Vaccine Introduction

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

2020 ◽  
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

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