No neutralizing effect of pre-existing tick-borne encephalitis virus antibodies against severe acute respiratory syndrome coronavirus-2: a prospective healthcare worker study

AbstractCertain immunizations including vaccination against tick-borne encephalitis virus (TBEV) have been suggested to confer cross-protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with ≥ 1 previous TBEV vaccination (n = 2018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7–1.0, P = 0.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p = 0.001) and total IgG (P < 0.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that the observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 infection is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations.

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Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response

Ticks and Tick-borne Diseases ◽

10.1016/j.ttbdis.2013.07.009 ◽

2014 ◽

Vol 5 (1) ◽

pp. 21-28 ◽

Cited By ~ 29

Author(s):

Pontus Lindblom ◽

Peter Wilhelmsson ◽

Linda Fryland ◽

Johanna Sjöwall ◽

Mats Haglund ◽

...

Keyword(s):

Clinical Response ◽

Encephalitis Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus

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Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2019-3-4-559-567 ◽

2019 ◽

Vol 9 (3-4) ◽

pp. 559-567

Author(s):

G. N. Leonova ◽

O. S. Majstrovskaya ◽

V. A. Lubova ◽

N. B. Sanina

Keyword(s):

Ex Vivo ◽

Experimental Studies ◽

Encephalitis Virus ◽

Virus Elimination ◽

Specific Antibodies ◽

Tick Borne Encephalitis ◽

Antibody Titers ◽

Tick Borne Encephalitis Virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.

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Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes

Journal of Virology ◽

10.1128/jvi.75.17.8259-8267.2001 ◽

2001 ◽

Vol 75 (17) ◽

pp. 8259-8267 ◽

Cited By ~ 58

Author(s):

Alexander G. Pletnev ◽

Michael Bray ◽

Kathryn A. Hanley ◽

Jim Speicher ◽

Randy Elkins

Keyword(s):

Virus Vaccine ◽

Rhesus Monkeys ◽

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Limit Of Detection ◽

Encephalitis Virus ◽

Live Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Highly Virulent

ABSTRACT Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 105 or 107 PFU of LGT strain TP21, with 105 PFU of DEN4, or with 103, 105, or 107 PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera by mosquitoes was addressed by inoculating a nonhematophagous mosquito,Toxorhynchites splendens, intrathoracically with the chimera or its DEN4 or LGT parent. Neither the LGT TP21/DEN4 vaccine candidate nor the wild-type LGT TP21 virus was able to infect this mosquito species, which is highly permissive for dengue viruses. Certain properties of the chimera, notably its attenuation for monkeys, its immunogenicity, and its failure to infect a highly permissive mosquito host, make it a promising vaccine candidate for use in immunization against severe disease caused by many tick-borne flaviviruses.

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In Vitro Characterization of the Innate Immune Pathways Engaged by Live and Inactivated Tick-Borne Encephalitis Virus

Vaccines ◽

10.3390/vaccines9060664 ◽

2021 ◽

Vol 9 (6) ◽

pp. 664

Author(s):

Aurora Signorazzi ◽

Jeroen L. A. Pennings ◽

Marilena P. Etna ◽

Malou Noya ◽

Eliana M. Coccia ◽

...

Keyword(s):

Pattern Recognition ◽

Mononuclear Cells ◽

Pattern Recognition Receptors ◽

Encephalitis Virus ◽

Innate Immune ◽

Interferon Response ◽

Live Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) infection can lead to inflammation of the central nervous system. The disease can be effectively prevented by whole inactivated virus vaccines. Here, we investigated the innate immune profile induced in vitro by the antigen component of the vaccines, inactivated TBEV (I-TBEV), to gain insights into the mechanism of action of the TBE vaccine as compared to the live virus. To this end, we exposed human peripheral blood mononuclear cells (PBMCs) to inactivated and live TBEV and assessed cellular responses by RNA sequencing. Both inactivated and live TBEV significantly induced an interferon-dominated gene signature and an increased RIG-I-like receptor (RLR) expression. Using pathway-specific inhibitors, we assessed the involvement of pattern recognition receptors in the sensing of inactivated or live TBEV. Only RLR pathway inhibition significantly suppressed the downstream cascade induced by I-TBEV, while responses to the replicating virus were impacted by the inhibition of RIG-I-like, as well as Toll-like, receptors. Our results show that inactivated and live TBEV predominantly engaged an interferon response in our in vitro PBMC platform, and indicate RLRs as the main pattern recognition receptors involved in I-TBEV sensing.

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TBE in South Korea

Tick-borne encephalitis - The Book ◽

10.33442/978-981-14-0914-1_12b-31 ◽

2019 ◽

Author(s):

Joon Young Song

Keyword(s):

South Korea ◽

Human Case ◽

Encephalitis Virus ◽

Surveillance Studies ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus

Although no human case of tick-borne encephalitis (TBE) has been documented in South Korea to date, surveillance studies have been conducted to evaluate the prevalence of tick-borne encephalitis virus (TBEV) in wild ticks.

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