Anti-idiotype antibody against pre-membrane-specific antibody as an adjunct to current dengue vaccination strategy

Dengue is a rapidly emerging vector-borne viral disease of humans transmitted by mosquitoes of the genus Aedes. Dengue viruses are divided into five antigenically distinct serotypes, DENV-1 to -5. The disease is endemic in over 130 countries, placing almost half of the world’s population at risk. Clinical disease presents as either a mild self-limiting infection or severe complications. Recovery from primary infection by one serotype provides life-long immunity against reinfection by that particular serotype whereas with subsequent infections by other serotypes the risk of developing severe dengue is increased. In contrast to previous understanding that immature dengue virus particles are non-infective it was shown recently that they become highly infectious in the presence of antibodies raised to the pre-membrane protein, prM, of the virion. While no licensed dengue treatment is currently available, several prototype vaccines are being evaluated in clinical studies. Most of these vaccine candidates contain native dengue prM, the presence of which can have the opposite effect to that desired by making immature dengue particles infective. This occurs through a mechanism of prM-specific antibody-dependent enhancement of infection. Hence, in order to safeguard patient welfare when designing future dengue vaccine constructs, provision of another anti-idiotype antibody that binds to and blocks the pathogen-activating region of anti-prM antibody, thus rendering it inactive, should be considered as an adjunct therapy. This strategy would have a potentially significant benefit by reducing cases of secondary infection, which is the major cause of dengue morbidity and mortality.