title: Safety, immunogenicity and efficacy of a recombinant tetravalent dengue vaccine: a meta-analysis of randomized trials.
abstract: The World Health Organization has stipulated a target: reduce the mortality rate caused by dengue disease by 50% until 2020. Most likely, this goal can be achieved by means of a dengue vaccine. Accordingly, the recombinant and tetravalent dengue vaccine (CYD-TDV), developed by the Sanofi Pasteur Group, is in an advanced stage of human testing. Although there are multiple randomized, placebo-controlled trials evaluating the CYD-TDV, individual results may have little power to identify differences between the populations studied. Thus, we conducted a meta-analysis to determine a more precise estimate of the overall parameters of safety, immunogenicity and efficacy of CYD-TDV. A data search was conducted in the PubMed, Medline, Cochrane Central Register of Controlled Trials and SciELO databases with defined selection criteria. We included for meta-analysis seven randomized and placebo-controlled studies that included 6678 patients randomized to receive the CYD-TDV (4586) or placebo (2092). Regarding vaccine safety, it was found that there was no significant difference between treated and placebo groups, as only approximately 5.5% of patients were withdrawn from the study. Regarding immunogenicity, the levels of neutralizing antibodies were measured by weighted mean differences (WMD), which were always higher in the vaccinated group (WMD/DENV1=59.7, 95% confidence interval [CI] 57-61; WMD/DENV2=99, 95% CI 95-102; WMD/DENV3=138, 95% CI 133-142; WMD/DENV4=123, 95% CI 119-126). The clinical efficacy of the vaccine was 59% (95% CI 15-80; RR=0.41, 95% CI 0.2-0.85, I(2)=30.9%). In conclusion, safety and a balanced immune response to the CYD-TDV were found. However, to fully establish the clinical effectiveness and robustness of immunogenicity, it is necessary to perform further studies to assess the long-term effects of the vaccine.
authors.affiliation: Virology Laboratory, Federal University of Goiás, BR 364 Km 192. Pq Industrial 3800, 75801615 Jataí, GO, Brazil. Electronic address: vivbiom@gmail.com.
authors.forename: Vivaldo G
authors.initials: VG
authors.lastname: da Costa
authors.affiliation: Virology Laboratory, Federal University of Goiás, BR 364 Km 192. Pq Industrial 3800, 75801615 Jataí, GO, Brazil.
authors.forename: Ariany C
authors.initials: AC
authors.lastname: Marques-Silva
authors.affiliation: Virology Laboratory, Federal University of Goiás, BR 364 Km 192. Pq Industrial 3800, 75801615 Jataí, GO, Brazil.
authors.forename: Vitor G
authors.initials: VG
authors.lastname: Floriano
authors.affiliation: Virology Laboratory, Federal University of Goiás, BR 364 Km 192. Pq Industrial 3800, 75801615 Jataí, GO, Brazil. Electronic address: mlmoreli@jatai.ufg.br.
authors.forename: Marcos L
authors.initials: ML
authors.lastname: Moreli
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000517:prevention & control; D053059:Dengue Vaccines / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D008962:Models, Theoretical; D016032:Randomized Controlled Trials as Topic; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014614:Vaccines, Synthetic
keywords: CYD-TDV; Dengue vaccine; Efficacy; Immunogenicity; Meta-analysis; Safety