Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials

Abstract

Significance Dengue virus (DENV) vaccine development is complicated by the existence of four genetically diverse DENV serotypes. A high degree of antigenic match between vaccine strains and circulating DENVs may be important to achieve high vaccine efficacy (VE). Using data from two phase 3 trials of the CYD-TDV vaccine, we assessed whether and how VE against virologically confirmed dengue varied with amino acid sequence characteristics and genotypes of the disease-causing DENVs. VE decreased with the degree of amino acid dissimilarity between the vaccine insert and disease-causing DENVs. After accounting for differential VE by serotype, this effect seemed to occur only for younger children, who also had lower baseline seropositivity and potentially a less broadly protective immune response.