Abstract
Dengue virus (DENV), the causative agent of dengue disease, is among the most important mosquito-borne pathogens worldwide. DENV is composed of four closely related serotypes and belongs to the Flaviviridae family alongside other important arthropod-borne viral pathogens such as Zika virus (ZIKV), West Nile virus (WNV) and Yellow Fever virus (YFV). After infection, the antibody response is mostly directed to the viral E glycoprotein which is composed of three structural domains named DI, DII and DIII that share variable degrees of homology among different viruses. Recent evidence supports a close serological interaction between ZIKV and DENV. The possibility of worse clinical outcomes as a consequence of antibody-dependent enhancement of infection (ADE) due to cross-reactive antibodies with poor neutralisation activity is a matter of concern. We tested polyclonal sera from groups of female Balb/C mice vaccinated with DNA constructs expressing DI/DII, DIII or the whole sE from different DENV serotypes and compared their activity in terms of cross-reactivity, neutralisation of virus infection and ADE. Our results indicate that the polyclonal antibody responses against the whole sE protein are highly cross-reactive with strong ADE and poor neutralisation activities due to DI/DII immunodominance. Conversely, anti-DIII polyclonal antibodies are type-specific, with no ADE towards ZIKV, WNV and YFV, and strong neutralisation activity restricted only to DENV.
Highlights
Dengue virus (DENV) is one of the most important human viral pathogens worldwide [1]
Anti-soluble E (sE) antibodies from mice immunised with DENV3 sE, showed low antiDIII activity with most of the antibody response directed against domains I and II (DI/DII) [38], in agreement with previous studies [19, 44]
Activities of DENV E DI and DII (DI/DII) and DIII DNA-vaccines are 15–80 times more frequent in secondary infections, and pre-existing heterotypic DENV antibodies are found in almost all patients with severe disease [25]
Summary
Dengue virus (DENV) is one of the most important human viral pathogens worldwide [1]. The disease is endemic in tropical regions around the world, with more than 3.9 billion people at primary risk of infection; current estimates indicate that around 390 million people have DENV infections each year which result in more than 96 million symptomatic cases [2].
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