Background: India is hyperendemic to dengue and over 50% of adults are seropositive. There is limited information on the association between neutralizing antibody profiles from prior exposure and viral RNA levels during subsequent infection.
Methods: Samples collected from patients with febrile illness was used to assess seropositivity by indirect ELISA. Dengue virus (DENV) RNA copy numbers were estimated by quantitative RT-PCR and serotype of the infecting DENV was determined by nested PCR. Focus reduction neutralizing antibody titer (FRNT) assay was established using Indian isolates to measure the levels of neutralizing antibodies and also to assess the cross-reactivity to related flaviviruses namely Zika virus (ZIKV), Japanese encephalitis virus (JEV) and West Nile virus (WNV).
Results: In this cross-sectional study, we show that dengue seropositivity increased from 52% in the 0-15 years group to 89% in >45 years group. Antibody levels negatively correlate with dengue RNAemia on the day of sample collection and higher RNAemia is observed in primary dengue as compared to secondary dengue. The geometric mean FRNT50 titers for DENV-2 is significantly higher as compared to the other three DENV serotypes. We observe cross-reactivity with ZIKV and significantly lower or no neutralizing antibodies against JEV and WNV. The FRNT50 values for international isolates of DENV-1, DENV-3 and DENV-4 is significantly lower as compared to Indian isolates.
Conclusions: Majority of the adult population in India have neutralizing antibodies to all the four DENV serotypes which correlates with reduced RNAemia during subsequent infection suggesting that antibodies can be considered as a good correlate of protection.
India is one of the hotspots of dengue infection. The objective of the study was to assess whether having previous exposure to dengue virus could influence how the body will respond to repeat infections with dengue virus. Here, we analysed samples from febrile patients to measure the amount of dengue virus genetic material in the blood, the type of virus and the amount of antibodies, which are proteins produced by the host in response to dengue virus infection. The majority of patient samples demonstrated the capability to restrict all four types of dengue virus in circulation within the country, but reduced capacity to restrict when it comes to international dengue virus types. These data will help to inform future dengue vaccine design and clinical studies in India.
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