Safety and Immunogenicity of a Recombinant Tetravalent Dengue Vaccine in 9–16 Year Olds

Abstract

CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9-16 year olds in Latin America. These findings support the continued development of CYD-TDV.

Clinical Presentation of Dengue by Serotype and Year of Epidemic in Martinique

“…Specifically, regarding the patients who developed virologically confirmed dengue, the proportion of patients with plasma leakage was 5.3% in vaccinees and 4.8% in control and no DSS case was observed in vaccinees as compared with two cases in control 3 ; interestingly, in another Phase II trial, the Sanofi Pasteur vaccine showed an anecdotal breakthrough case protection against DENV-2. 4 Another mechanism could be the acquisition of specific virulence by certain viral strains. The problem is not well documented.…”

“…In addition to potentially providing insight into dengue pathogenesis, identifying any serotypespecific differences is of interest in light of the Sanofi Pasteur Phase II vaccine trials, which suggest different levels of protection against the four serotypes. 3,4 …”

“…The circulating dengue serotypes (DENV-1 to -4) have been closely monitored since January 1995. 1 The DENV-2 infections were recorded continuously over time, whereas infections by the other serotypes have had the characteristic to emerge periodically, such as DENV- 4 It is recognized that, whatever the serotype, primary dengue infection is most often asymptomatic or only mildly symptomatic, and provides immunity against re-infection by that serotype. 2 Subsequent infection by another serotype (secondary infection) can lead to more severe clinical forms.…”

The yellow fever 17D virus as a platform for new live attenuated vaccines

“…Early in 2011, the vaccine was administered to over 6000 children and adults from endemic and non-endemic areas with no questions regarding its safety. 41,42,46 A phase IIb clinical trial in 2669 Thai schoolchildren with the tetravalent vaccine showed poor efficacy (30.3%) of protection against febrile DEN infections. 45 While vaccination reduced incidence of DEN1, DEN3, and DEN4 by 90%, the protection against DEN2 was low (9.2%), downgrading overall protection.…”

“…39 These recombinant live attenuated chimeric viruses have been tested in man to different extents, and due to the inexistence of any alternative, particular attention has been devoted to the immunogenicity and safety of the YF17D-DV tetravalent vaccine. [40][41][42][43][44][45][46] The live attenuated chimeric 17D-DEN tetravalent vaccine candidate from Sanofi-Pasteur constitutes the most tested dengue vaccine possibility. The chimeric viruses proved to be genetically and phenotypically stable, 47 less virulent when compared with the yellow fever vaccine 17D and unable to infect mosquitoes orally.…”