Flavivirus-induced antibody cross-reactivity

Dengue virus A number of flaviviruses constitute a significant threat to global health. Dengue virus (DENV) infection causes around 21,000 human deaths annually, and it is estimated that at least 120 countries have endemic DENV transmission, whilst in recent years, West Nile virus (WNV) has become more prominent as a zoonotic agent, particularly in North America where the virus first emerged in 1999 and rapidly spread across the continent. WNV has now emerged in a number of European countries, particularly around the Mediterranean basin, where infections in humans, horses and birds have been reported.

Cross-reactivity of sera raised against one flavivirus recognising another flavivirus has been well documented. One consequence of flavivirus cross-reactivity is the occurrence of false-positive results, yet cross-reactivity can lead to cross-protection. Understanding and manipulating the cross-reactive properties of flaviviruses has the potential to assist the development of effective broad-spectrum human vaccines against WNV and other existing and emerging flaviviruses.

 

Flavivirus-induced antibody cross-reactivity. J Gen Virol. Sep 7 2011
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 neutralisation test. Neutralisation of Louping ill virus (LIV) occurred, but no significant neutralisation of Murray Valley encephalitis virus (MVEV) was observed. Sera from some individuals vaccinated against TBEV and JEV neutralised WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralised DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralisation 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 exists between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

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