Efficacy after 1 and 2 doses of CYD-TDV in dengue endemic areas by dengue serostatus

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine

“…In the case-cohort study of 3 CYD-TDV efficacy studies, the cumulative incidence of severe VCD over a period of 60 months was 0.40% among dengue seronegative participants, who had received all 3 CYD-TDV doses, 12 where the third dose has been shown to further increase the immune response in baseline dengue seronegative participants. 31 , 32 The proportion of hospitalized VCD cases in seropositive participants were similar between this [0.32% (2/629)] and the case-cohort (0.38%) studies. 12 Overall, the reported safety outcomes were generally consistent with published safety profiles.…”

Dengue vaccine breakthrough infections reveal properties of neutralizing antibodies linked to protection

“…Dengvaxia developed NAbs to DENV1 and 3, yet vaccine efficacy against these two serotypes was low (6). We characterized the properties of vaccine induced Abs in baseline seronegative children who subsequently experienced DENV1 (n=15 subjects) or 3 (n=18 subjects) breakthrough infections (Supplementary Table 2).…”

“…Several DENV vaccines are at different stages of clinical development (2)(3)(4). While the development of DENV vaccines has been guided by the presence of NAbs as a correlate of protection, recent studies indicate that NAbs to the four serotypes after vaccination is not a reliable correlate of protection (5)(6)(7). We compared the properties of NAbs induced by wild type DENV serotype 1 and 3 infections and a leading vaccine (Dengvaxia developed by Sanofi Pasteur) to improve our understanding of the properties of protective Abs.…”

“…Efficacy was high in children with pre-existing immunity to DENVs who received the vaccine. In DENV-naïve children, the vaccine reliably stimulated NAbs to the 4 serotypes, yet overall efficacy was low (6,16). More recently, preliminary efficacy data from another clinical trial (TAK-003 developed Takeda) also indicate that the presence of vaccine induced NAb alone is not a reliable indicator of protection in children who were DENV seronegative at baseline (5).…”

Design of Monovalent and Chimeric Tetravalent Dengue Vaccine Using an Immunoinformatics Approach

“…Numerous DENV vaccine candidates are in various phases of clinical development (de Alwis et al 2011 ; Guzman et al 2007 ; Mathew et al 2011 ). While the existence of NAbs as a correlate of protection has led the development of DENV vaccines, new research reveals that the presence of NAbs to the four serotypes following vaccination is not a reliable predictor of protection (Biswal et al 2020 ; Dayan et al 2020 ; Moodie et al 2018 ). Dengvaxia is a live attenuated chimeric tetravalent dengue vaccine (CYD-TDV) produced by altering the live attenuated yellow fever 17D vaccine to include the envelope (E) and premembrane proteins of each DENV serotype (Thomas and Yoon 2019 ).…”