Study of mature dengue virus-like particles as new dengue vaccine candidate

Abstract

Our study of different human monoclonal antibodies showed that compared with group reactive anti-fusion loop monoclonal antibodies, type specific antidomain III monoclonal antibodies have higher epitope accessibility and binding avidity to mature virus-like particles (VLPs), which presumably representing mature dengue virus (DENV) virions, the major infectious component in mixed DENV particles in culture. These findings not only suggest that type specific antibodies such as anti-domain III antibodies, though present as a small proportion of anti-envelope antibodies in polyclonal human serum, may contribute greatly to neutralizing activity, but also highlight the importance of inducing this type specific anti-domain III antibodies by using mature particles for vaccine strategy. Using DNA vaccines to test our hypothesis, we showed that DNA vaccine expressing mature VLPs could induce similar anti-DENV antibodies, neutralizing antibodies, less anti-fusion loop antibodies, no or little anti-precursor membrane antibodies compared with DNA vaccine expressing mixed VLPs. Future studies are needed to verify that mature DENV particles are better vaccine candidates than mixed DENV particles.