Barriers to Effective Dengue Vaccination, Cross Reactions and Immune Responses: A Review

Abstract

One of the most prevalent diseases spread by the mosquitoes in the world is the dengue fever which is a major health issue to the people of the tropical and subtropical regions. They have approximated that 390 million people annually are infected by dengue virus (DENV) of which approximately 96 million get into clinical conditions. Besides, health impacts, dengue has a high cost, and this is in the economic sphere. In contemporary times, there exist no specific antiviral drugs and the only approved vaccine given is protection to seropositive (had been exposed to dengue before) and not seronegative (dengue naive) patients. This review explores the key immune responses and their interaction with DENV and the current innovations in the production of vaccines. The mechanisms through which the vaccines may work are also addressed e.g. preexisting immunity, and the long-term barriers to an effective vaccine: antigenic diversity of four DENV serotypes, antibody-dependent enhancement (ADE) and cross- reactivity to related flaviviruses. Finally, we mention the therapeutic potential of targeting T follicular helper (Tfh) cells as critical controllers of the production of high-affinity antibodies as a means of improving vaccine response irrespective of whether the individual had been previously exposed to dengue.