A Secretion Deficiency Mutant Vaccine against Dengue Virus I Induces Durable Immunity and Confers Protection against Dengue Virus II

The antibody dependent enhancement (ADE) potential of dengue virus (DENV) has made the development of an effective vaccine a global health priority1-5. Here, we generate two DNA DENV vaccine that encode for pre-membrane (prM) and envelope (E) proteins with secretion deficiency mutant (DNSP) and full-length prME protein wild type (WT). Both vaccines induce cell-mediated immune responses and prevent lethality after DENV1 challenge in mice. Immunization of DNSP induces almost none antibodies against prME protein and confers durable protection as evidenced by T cell responses and challenge studies 1 year later. In vitro models of DENV infection, DNSP reduces K562 cells infection rate in four serotypes of DENV. In vivo models of DENV2 infection, DNSP provides effective protection against DENV2 infection. The DNA vaccine platform encoding secretion deficiency mutant prME genes is a promising candidate for enhancing cell-mediated immune responses and reducing antibodies production. DNSP vaccine can be used as a booster, has the potential to reduce the ADE effect.