CYD Tetravalent Dengue Vaccine Performance by Baseline Immune Profile (Monotypic/Multitypic) in Dengue-Seropositive Individuals

Abstract

Background The immune profile of dengue-experienced individuals is a determinant of dengue reinfection severity risk. Individuals with a single prior dengue infection (monotypic) are at highest risk for severe disease, while individuals with ≥ 2 prior dengue infections (multitypic) are at lower risk. The tetravalent dengue vaccine (CYD-TDV) has shown efficacy in the prevention of dengue in individuals with prior dengue infection. We estimated efficacy in individuals with monotypic or multitypic immune profiles. Methods Participants enrolled in the immunogenicity subsets of 2 randomized placebo-controlled phase 3 studies (CYD14, NCT01373281; CYD15, NCT01374516) were classified as either monotypic or multitypic, based on measured baseline dengue plaque reduction neutralization test. Vaccine efficacy (VE) against symptomatic virologically confirmed dengue (VCD) was assessed over 25 months and against VCD hospitalization over 6 years. Results Of 3927 participants in the immunogenicity subsets, 496 and 257 in the CYD-TDV and placebo groups, respectively, were classified as monotypic immune, and 1227 and 612, respectively, as multitypic immune. VE against symptomatic VCD was 77.4% (95% CI, 56.4%–88.2%) for monotypic and 89.2% (95% CI, 71.5%–95.9%) for multitypic profiles, with corresponding absolute risk reductions (ARRs) of 4.48% (95% CI, 2.32%–6.65%) for monotypics and 1.67% (95% CI, .89%–2.46%) for multitypics. VE against hospitalized VCD was 75.3% (95% CI, 42.7%–90.2%) in monotypics and 81.2% (95% CI, 21.7%–96.8%) in multitypics, with ARRs of 0.95% (95% CI, .37%–1.53%) for monotypics and 0.18% (95% CI, .02%–.34%) for multitypics. Conclusions CYD-TDV benefits individuals with monotypic and multitypic immune profiles. Larger public health benefit is expected to derive from the protection of individuals with a monotypic immune profile.

Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with a new dengue rapid diagnostic test: a retrospective analysis of phase 3 efficacy trials

“…21 It is worth noting that the CYD-TDV vaccine confers robust efficacy against severe dengue in individuals with both a pre-vaccination monotypic and multitypic immune profile. 22 The selection of an RDT for point-of-care prevaccination screening depends on several factors, such as accuracy, ease of use, and affordability. 8,17 As well as offering high specificity and sensitivity, the OnSite IgG RDT can be done within 25 min on whole blood, and thus might facilitate convenient testing and vaccination at the same visit, increasing compliance and uptake of CYD-TDV vaccination.…”

Envelope-dimer epitope-like broadly protective antibodies against dengue in children following natural infection and vaccination

“…It was previously thought that monotypic individuals would benefit most from Dengvaxia, as those with multitypic immunity were expected to be protected. However, a previous study showed similar Dengvaxia efficacy in monotypic and multitypic individuals 64 . Here, we observed a significant increase WT E protein and E dimer binding, neutralizing, and EDE-like Abs in both vaccinated and unvaccinated individuals, indicating a robust boosting of the immune response in both groups.…”

“…It was previously thought that monotypic individuals would benefit most from Dengvaxia, as those with multitypic immunity were expected to be protected. However, a previous study showed similar Dengvaxia efficacy in monotypic and multitypic individuals 64 .…”

Dengue vaccine development by the year 2020: challenges and prospects

“…It should also be affordable, simple to use and provide rapid results. Two recent comparative evaluations on currently available assays showed high specificity (>98%) for all immunoassays apart from one RDT, but variable sensitivities (higher sensitivities observed for the ELISAs [89% and 93%] than the RDTs [48–71%]) [ 23 • , 24 • ] Sensitivity appeared similar in samples from individuals with recent and remote virologically confirmed dengue (VCD). Cross-reactivity to other flaviviruses was low with RDTs (</ = 7%), but more significant with ELISAs (up to 51% for West Nile and 34% for Zika).…”