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

Maíra Aguiar,Nico Stollenwerk

doi:10.3390/vaccines8040674

Maíra Aguiar, Nico Stollenwerk

Open Access

https://doi.org/10.3390/vaccines8040674

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Abstract

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.

Highlights

Dengue fever is a viral mosquito-borne infection of major international public health concern, with approximately 3 billion people at risk of acquiring the infection
From our Bayesian analysis, vaccine efficacy estimations by serotype and serostatus are shown in Table 1 part
Vaccine efficacy against serotype 1 was observed to be slightly smaller in seronegative than in seropositive individuals

Summary

Introduction

Dengue fever is a viral mosquito-borne infection of major international public health concern, with approximately 3 billion people at risk of acquiring the infection. Caused by four antigenically related but distinct serotypes (DENV-1 to DENV-4), it is estimated that 390 million dengue infections occur every year, of which 96 million manifest symptoms with any level of disease severity [1]. Subsequent infections by any other of the 3 heterotypic serotypes increases the risk of developing severe dengue due to an immunological process called antibody-dependent enhancement (ADE) [2,3,4,5]. There is a compelling public health need for an effective preventive intervention against dengue. A safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control

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