The Interplay of Dengue Virus Morphological Diversity and Human Antibodies

Dengue virus (DENV) infects ∼400 million people annually, and there is no available vaccine or therapeutics. It is not clear why candidate vaccines provide only modest protection. In addition to the presence of four different dengue serotypes, there is also structural heterogeneity in DENV infectious particles, even within a strain. This severely complicates the development of vaccines and therapeutics. The currently known different morphologies of DENV are: immature, partially mature, compact mature, and expanded mature forms of the virus. In this review I describe these forms of the virus, their infectivity, and how antibodies could recognize these morphologies. I also discuss possible vaccine and antibody therapeutic formulations to protect against all morphologies. Dengue virus (DENV) infects ∼400 million people annually, and there is no available vaccine or therapeutics. It is not clear why candidate vaccines provide only modest protection. In addition to the presence of four different dengue serotypes, there is also structural heterogeneity in DENV infectious particles, even within a strain. This severely complicates the development of vaccines and therapeutics. The currently known different morphologies of DENV are: immature, partially mature, compact mature, and expanded mature forms of the virus. In this review I describe these forms of the virus, their infectivity, and how antibodies could recognize these morphologies. I also discuss possible vaccine and antibody therapeutic formulations to protect against all morphologies. Although dengue virus (DENV) infects approximately 400 million people annually, there are currently no effective therapeutics or a vaccine. Due to the potential of causing enhancement of disease, a DENV vaccine has to stimulate equal protective responses towards all four dengue serotypes. Additionally, the presence of different dengue virus morphologies within a strain may further complicate vaccine and therapeutic design. Antibodies may have different potencies against different DENV morphologies. A vaccine may need to represent all DENV morphologies. Antibody therapeutics should contain antibodies against all morphologies. Although dengue virus (DENV) infects approximately 400 million people annually, there are currently no effective therapeutics or a vaccine. Due to the potential of causing enhancement of disease, a DENV vaccine has to stimulate equal protective responses towards all four dengue serotypes. Additionally, the presence of different dengue virus morphologies within a strain may further complicate vaccine and therapeutic design. Antibodies may have different potencies against different DENV morphologies. A vaccine may need to represent all DENV morphologies. Antibody therapeutics should contain antibodies against all morphologies.