IMMUNE IMPRINTING BY PRIOR INFECTIONS: MECHANISMS LINKING ZIKA EXPOSURE TO SEVERE DENGUE DISEASE

Abstract

Zika virus and dengue virus are an important and a significant global health burden transmitted by mosquitoes. These viruses are often co-circulating in tropical and subtropical areas which makes it a high chance of sequential infection among populations that have been exposed to such viruses. There is growing evidence to the effect that being infected by one flavivirus may be instrumental in influencing immune responses to that of other related viruses. This is referred to as immune imprinting or original antigenic sin and can influence antibody and cellular responses in such a manner that it changes the severity of the disease. Specifically, the cross-reactive antibodies produced during the initial infection with the flaviviruses might not be able to neutralize second infection and instead promote viral entry into immune cells with Fc receptor-bearing via antibody-dependent enhancement (ADE). This process has also been closely linked to extreme cases of dengue including dengue hemorrhagic fever and dengue shock syndrome. The experimental and epidemiological literature also indicates that the immunological interaction between these two viruses is complicated because under some circumstances anti-body formation during these infections helps infectious cells multiply. Besides ADE, novel processes like viral entry by B-cell receptor and cross-reactive immune memory could have a part in the amplification of viral replication and immunopathology in sequential infections. Such immune responses pose a profound problem when attempting vaccines development because vaccines should induce body defenses but not cross-reactive immunoglobulins that can promote an infection. The following review provides an overview of existing information on the pathogenic processes of immune imprinting between Zika and dengue virus infection, with a focus on antibody-dependent enhancement, cross-reactive immunity, and some new avenues of immunology that could mediate disease severity. The elucidation of these mechanisms is important in making better it is essential in designing vaccines against flaviviruses, anticipating the risk of the disease in the endemic areas, and providing safer immunization protocols.