Dengue is a globally important disease caused by four serotypes of dengue virus. Dengue vaccine development has been hampered by antigenic cross-reactivity among serotypes, which potentially causes antibody-dependent enhancement of infection and disease severity. Here, we found that a single amino acid substitution in the envelope protein at position 87 from aspartic acid to asparagine or at 107 from leucine to phenylalanine is critical for suppressing induction of infection-enhancing antibody in a mouse model. The site and type of amino acid substitution were determined via neutralization escape using an enhancing activity-only monoclonal antibody that was engineered to reveal neutralizing activity. Mutated dengue type 1 DNA vaccines containing either or both amino acid substitution(s) induced neutralizing antibodies devoid of enhancing activity against all serotypes. The effect of substitution was further demonstrated using other serotypes and a tetravalent formulation. This finding may contribute to the development of infection enhancing activity-free dengue vaccines.

This article was published in iScience on March 2019.

Key Amino Acid Substitution for Infection-Enhancing Activity-Free Designer Dengue Vaccines.

Yamanaka A, Konishi E