Cross-reactive immunity involving either Japanese encephalitis virus or yellow fever virus
The flavivirus group contains medically important viruses that can illicit immune responses that are cross-reactive against other flaviviruses. These responses can be protective, sub-optimal or harmful upon heterologous infection or vaccination, based on the neutralising efficacy of clonally-expanded responses against the previous disease to the current challenge. It is important to categorise the immune consequences of each heterologous pairing in order to predict the disease consequences for individuals in co-endemic areas, and to aid in the design of heterologous vaccination regimes and cross-protective vaccines. This review characterises cross-reactive responses involving Japanese encephalitis virus (JEV) and yellow fever virus (YFV), West Nile virus (WNV), Zika virus (ZIKV) and dengue virus (DENV), and is the first to focus on those involving JEV or YFV.
Each flavivirus pairing had a unique functional immune outcome that was largely consistent between papers, however results were frequently differed between studies using murine models and studies of human sera. Prior JEV humoral immunity was shown to be protective against WNV infection in animal models but not in humans, whilst prior WNV humoral immunity likely gives protection against JEV. JEV-induced cellular immunity is described as protective against ZIKV, but this may not be enough to overcome humoral ADE, with the same effect being observed in the opposite direction. JEV immunity is protective against DENV infection but this may be outweighed by ADE, whilst prior DENV immunity may give protection against JEV infection. Prior JEV immunity gives protection against YFV infection but again there is evidence of ADE, whereas YFV immunity has no significant effect on subsequent JEV infection.
Regarding yellow fever, prior YFV immunity is likely protective against WNV infection, whereas WNV immunity may cause ADE of subsequent YFV infection. YFV immunity likely has no significant effect on subsequent ZIKV infection, and similarly ZIKV immunity is only slightly cross-reactive and likely not harmful in the face of YFV infection. YFV immunity likely has no significant effect on subsequent DENV infection, and DENV immunity has an unclear but potentially harmful effect on subsequent YFV infection.
Additional considerations such as the significance of the location of the targeted epitope on the functional immune outcome were detailed, and the general protective effect of more than one prior heterologous exposure was discussed. The implications of these results for cross-reactivity studies on the chimeric vaccine IMOJEV were explored, and comparisons made between the cross-reactive profiles of JEV, YFV and IMOJEV.
