Neutralizing antibodies from prior exposure negatively correlate with dengue viremia and may influence serotype dominance

Abstract

Abstract India is hyperendemic to dengue virus and over 50% of the adults are seropositive but there is limited information on the association between prior dengue exposure with neutralizing antibody profiles and how this could influence virus evolution and vaccine development. In this work, we found that the dengue seropositivity increased with age and pre-existing antibody levels negatively correlated with viremia during acute phase of illness. Adults showed a higher levels of viremia which associated with lower levels of neutralizing antibodies as compared to children. The titers of neutralizing antibodies negatively influenced the dominance of circulating dengue serotypes with highest levels of the neutralizing antibodies against DENV-2 followed by DENV-1, DENV-3 and DENV-4. We observed minimal cross-reactivity of neutralizing antibodies with related flaviviruses such as Japanese encephalitis virus and West Nile virus and the antibodies elicited against Indian isolates show a reduced ability to neutralize international dengue isolates.