Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials
Juraska M., Magaret CA., Shao J., Carpp LN., Fiore-Gartland AJ., Benkeser D., Girerd-Chambaz Y., Langevin E., Frago C., Guy B., Jackson N., Duong Thi Hue K., Simmons CP., Edlefsen PT., Gilbert PB.
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.