scholarly journals Flavivirus-induced antibody cross-reactivity

2011 ◽  
Vol 92 (12) ◽  
pp. 2821-2829 ◽  
Author(s):  
Karen L. Mansfield ◽  
Daniel L. Horton ◽  
Nicholas Johnson ◽  
Li Li ◽  
Alan D. T. Barrett ◽  
...  
Keyword(s):  
Yellow Fever Virus ◽  
Cross Reactivity ◽  
Encephalitis Virus ◽  
Antigenic Relationship ◽  
Tick Borne Encephalitis ◽  
History Of ◽  
Louping Ill ◽  
Tick Borne Encephalitis Virus ◽  
Antigenic Cartography ◽  
The Individual

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.

scholarly journals Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

2015 ◽  
Vol 22 (7) ◽  
pp. 754-760 ◽  
Author(s):  
Fabian H. Weissbach ◽  
Hans H. Hirsch
Keyword(s):  
Yellow Fever Virus ◽  
Cross Reactivity ◽  
Encephalitis Virus ◽  
Serological Testing ◽  
Negative Results ◽  
Tick Borne Encephalitis ◽  
Human Sera ◽  
Immunosorbent Assays ◽  
Tick Borne Encephalitis Virus ◽  
And Control

ABSTRACTDespite the availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European Centre for Disease Prevention and Control in the past 2 decades. Since the diagnosis of TBEV exposure relies on serological testing, we compared two commercial enzyme-linked immunosorbent assays (ELISAs), i.e., Immunozym FSME IgG assay (ELISA-1) and Euroimmun FSME Vienna IgG assay (ELISA-2). Both assays use whole TBEV antigens, but they differ in viral strains (Neudoerfl for ELISA-1 and K23 for ELISA-2) and cutoff values. In testing of samples from 398 healthy blood donors, ELISA-1 showed higher reactivity levels than ELISA-2 (P< 0.001), suggesting different assay properties. This finding was supported by Bland-Altman analysis of the optical density at 450 nm (OD450) (mean bias, +0.32 [95% limits of agreement, −0.31 to +0.95]) and persisted after transformation into Vienna units. Concordant results were observed for 276 sera (69%) (44 positive and 232 negative results). Discordant results were observed for 122 sera (31%); 15 were fully discordant, all being ELISA-1 positive and ELISA-2 negative, and 107 were partially discordant (101 being ELISA-1 indeterminate and ELISA-2 negative and 6 having positive or indeterminate reactivity in both ELISAs). Neutralization testing at a 1:10 dilution yielded positive results for 33 of 44 concordant positive sera, 1 of 15 fully discordant sera, and 1 of 33 partially discordant sera. Indirect immunofluorescence testing revealed high antibody titers of ≥100 for yellow fever virus in 18 cases and for dengue virus in one case, suggesting that cross-reactivity contributed to the ELISA-1 results. We conclude that (i) cross-reactivity among flaviviruses remains a limitation of TBEV serological testing, (ii) ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera, and (iii) neutralization testing is most specific and should be reserved for selective questions.

scholarly journals A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Cécile Beck ◽  
Philippe Desprès ◽  
Sylvie Paulous ◽  
Jessica Vanhomwegen ◽  
Steeve Lowenski ◽  
...  
Keyword(s):  
High Performance ◽  
Neurological Diseases ◽  
Expression System ◽  
Cross Reactivity ◽  
Encephalitis Virus ◽  
Serological Tests ◽  
Multiplex Immunoassay ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Negative Controls

West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using theDrosophilaS2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases.

scholarly journals The serological response and long-lasting resistance against infection with louping-ill virus in sheep immunized with a highly attenuated tick-borne encephalitis virus

1969 ◽  
Vol 67 (4) ◽  
pp. 731-738 ◽  
Author(s):  
V. Mayer ◽  
D. Blaškovič ◽  
E. Ernek ◽  
H. Libíková
Keyword(s):  
Neutralizing Antibodies ◽  
Encephalitis Virus ◽  
Serological Response ◽  
Immune Control ◽  
Summer Period ◽  
Tick Borne Encephalitis ◽  
Louping Ill ◽  
Tick Borne Encephalitis Virus

SUMMARYThe vaccination of sheep with one dose of the monkey-and mouse-attenuated tick-borne encephalitis virus (the Hy-HK 28 ‘2’ clone) causes seroconversion from negative into positive in 85% of animals. In sheep with pre-existing virus-neutralizing antibodies and increas of their titres was observed in 81%. The antibodies persisted for at least 12 months after the vaccination and during the summer period of grazing the number of serologically positive animals even increased.The vaccinated animals, in contrast to the non-immune control sheep, developed no viraemia after challenge with the virulent louping-ill virus, performed 11 months after immunization.

Tick-borne encephalitides

2011 ◽  
Author(s):  
Patricia A. Nuttall
Keyword(s):  
North America ◽  
Tick Species ◽  
Encephalitis Virus ◽  
Virus Family ◽  
Wild Mammals ◽  
Tick Borne Encephalitis ◽  
Powassan Virus ◽  
Louping Ill ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

Tick-borne encephalitides are caused by three different viruses transmitted by ticks and belonging to the Flaviviridae virus family: tick-borne encephalitis virus (Far Eastern, Siberian, and European subtypes), louping ill virus, and Powassan virus (including deer tick virus). These viruses cause encephalitis affecting humans in Eurasia and North America. In nature, they are maintained in transmission cycles involving Ixodes tick species and small or medium-sized wild mammals. The tick-borne flavivirus group is one of the most intensely studied groups of tick-borne pathogens.

scholarly journals Molecular Basis of a Protective/Neutralizing Monoclonal Antibody Targeting Envelope Proteins of both Tick-Borne Encephalitis Virus and Louping Ill Virus

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Xu Yang ◽  
Jianxun Qi ◽  
Ruchao Peng ◽  
Lianpan Dai ◽  
Ernest A. Gould ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Encephalitis Virus ◽  
Infection Rates ◽  
E Proteins ◽  
E Protein ◽  
Tick Borne Encephalitis ◽  
The Family ◽  
Lateral Ridge ◽  
Louping Ill ◽  
Tick Borne Encephalitis Virus

ABSTRACT Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are members of the tick-borne flaviviruses (TBFVs) in the family Flaviviridae which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized. Here, we determined the crystal structures of the LIV envelope (E) protein and report the comparative structural analysis of a TBFV broadly neutralizing murine MAb (MAb 4.2) in complex with either the LIV or TBEV E protein. The structures reveal that MAb 4.2 binds to the lateral ridge of domain III of the E protein (EDIII) of LIV or TBEV, an epitope also reported for other potently neutralizing MAbs against mosquito-borne flaviviruses (MBFVs), but adopts a unique binding orientation. Further structural analysis suggested that MAb 4.2 may neutralize flavivirus infection by preventing the structural rearrangement required for membrane fusion during virus entry. These findings extend our understanding of the vulnerability of TBFVs and other flaviviruses (including MBFVs) and provide an avenue for antibody-based TBFV antiviral development. IMPORTANCE Understanding the mechanism of antibody neutralization/protection against a virus is crucial for antiviral countermeasure development. Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are tick-borne flaviviruses (TBFVs) in the family Flaviviridae. They cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines for both viruses are available, infection rates are rising due to low vaccination coverage. In this study, we solved the crystal structures of the LIV envelope protein (E) and a broadly neutralizing/protective TBFV MAb, MAb 4.2, in complex with E from either TBEV or LIV. Key structural features shared by TBFV E proteins were analyzed. The structures of E-antibody complexes showed that MAb 4.2 targets the lateral ridge of both the TBEV and LIV E proteins, a vulnerable site in flaviviruses for other potent neutralizing MAbs. Thus, this site represents a promising target for TBFV antiviral development. Further, these structures provide important information for understanding TBFV antigenicity.

scholarly journals Experience of application of IgY-technology for laboratory diagnostics of viral infections

2020 ◽  
Vol 65 (1) ◽  
pp. 21-26 ◽  
Author(s):  
A. P. Ivanov ◽  
T. D. Klebleeva ◽  
O. E. Ivanova
Keyword(s):  
Yellow Fever ◽  
Viral Infections ◽  
Yellow Fever Virus ◽  
Laboratory Diagnosis ◽  
Encephalitis Virus ◽  
Fever Virus ◽  
Laboratory Animals ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Introduction. The well-known advantages of class Y antibodies (IgY) from egg yolks of immunized hens in comparison with class G antibodies (IgG) of laboratory animals traditionally used in laboratory diagnosis of infectious diseases determine the stable interest of researchers in using IgY for these purposes (IgY technology) . Over the past 20 years, the obvious benefits of IgY technology have been demonstrated for a number of viral and bacterial infections. Goals and objectives. Construction of ELISA systems based on specific IgY for laboratory diagnosis of infections caused by tick-borne encephalitis virus, yellow fever virus, poliovirus.Material and methods. Obtaining yolk preparations of immunized chickens, obtaining highly purified IgY preparations (salting out, affinity chromatography), constructing ELISA systems for determining virus-specific antigens, testing the parameters of ELISA systems.Results and discussion. For the first time in laboratory practice, ELISA systems based on the use of specific polyclonal IgY were designed for laboratory diagnosis of topical human viral infections caused by flaviviruses and enteroviruses: determination of antigens of tick-borne encephalitis virus, yellow fever virus, 3 types of poliovirus. It was experimentally shown that these ELISA systems have high sensitivity and specificity, which allows them to be used for the semiquantitative and quantitative determination of antigens of these viruses in various materials (infected cell cultures, vaccines, etc.).Conclusion. The ELISA systems developed on the basis of specific IgY for determination of viral antigens can be effectively used for laboratory diagnosis of a number of viral infections, for the validation and control of vaccine preparations.

scholarly journals Tick-borne encephalitis virus (TBEV) – findings on cross reactivity and longevity of TBEV antibodies in animal sera

2014 ◽  
Vol 10 (1) ◽  
pp. 78 ◽  
Author(s):  
Christine Klaus ◽  
Ute Ziegler ◽  
Donata Kalthoff ◽  
Bernd Hoffmann ◽  
Martin Beer
Keyword(s):  
Cross Reactivity ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus
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