Flavivirus-induced antibody cross-reactivity

Karen L Mansfield,Li Li,Nicholas Johnson,Sareen E Galbraith,Daniel L Horton,Anthony R Fooks,Derek J Smith,Tom Solomon,Alan D T Barrett

doi:10.1099/vir.0.031641-0

Abstract

Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

Highlights

Within the family Flaviviridae, the genus Flavivirus comprises tick-borne, mosquito-borne and no-knownvector viruses, and virus species are further placed into groups with shared antigenic cross-reactivity (Porterfield, 1980)
Despite being from volunteers only vaccinated against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and in some cases yellow fever virus (YFV), most sera had detectable titres against louping ill virus (LIV) and some had titres against West Nile virus (WNV) and Dengue viruses (DENV)-2
Using these sera, JEV was antigenically closer to TBEV than WNV, whilst WNV was in close proximity to DENV-2

Summary

Introduction

Within the family Flaviviridae, the genus Flavivirus comprises tick-borne, mosquito-borne and no-knownvector viruses, and virus species are further placed into groups with shared antigenic cross-reactivity (Porterfield, 1980). Other serocomplexes include yellow fever virus (YFV), Dengue virus (DENV) and tick-borne encephalitis virus (TBEV), which contains three subtypes of TBEV and louping ill virus (LIV) (Porterfield, 1980; Calisher et al, 1989). WNV has emerged in a number of European countries, around the Mediterranean basin, where infections in humans, horses and birds have been reported (Hubalek et al, 1999; Murgue et al, 2001; Autorino et al, 2002; Bakonyi et al, 2006; Krisztalovics et al, 2008; Rizzo et al, 2009). A substantial number of human infections have recently been detected in Greece

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