Complexity of neutralization antibodies against multiple dengue viral serotypes after heterotypic immunization and secondary infection revealed by in-depth analysis of cross-reactive antibodies.
Tsai WY, Durbin A, Tsai JJ, Hsieh SC, Whitehead S, Wang WK.
Tsai WY, Durbin A, Tsai JJ, Hsieh SC, Whitehead S, Wang WK. (2015) Complexity of neutralization antibodies against multiple dengue viral serotypes after heterotypic immunization and secondary infection revealed by in-depth analysis of cross-reactive antibodies. Journal of Virology 89(14):7348-7362.
The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Despite the presence of neutralizing antibodies, a moderate efficacy was recently reported in Phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing antibodies in polyclonal human sera is urgently needed. We studied vaccinees who received heterotypic immunization of live-attenuated vaccines as cases with known first and second DENV serotypes exposed. We found anti-envelope antibodies consist of group-reactive (GR), complex-reactive (CR) and type-specific (TS) antibodies; both GR and CR antibodies contribute significantly to multitypic neutralizing activities after secondary DENV immunization. These findings have implications for alternative strategies for DENV vaccination. Certain TS antibodies were recently discovered to contribute to the monotypic neutralizing activity and protection after primary DENV infection; our findings of the complexity of neutralizing activities after secondary immunization/infection provide new insights into neutralizing antibodies as surrogates of protection.