scholarly journals Comparison of the Immunogenicity and Safety of Two Pediatric TBE Vaccines Based on the Far Eastern and European Virus Subtypes

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mikhail F. Vorovitch ◽  
Galina B. Maikova ◽  
Liubov L. Chernokhaeva ◽  
Victor V. Romanenko ◽  
Galina G. Karganova ◽  
...  

Up to 10,000 cases of tick-borne encephalitis are registered annually, 20% of which occur in children under 17 years of age. A comparison of the immunogenicity and safety between a new pediatric Tick-E-Vac vaccine based on the TBEV strain Sofjin and FSME-IMMUN Junior vaccine was performed in the Sverdlovsk region. The vaccine strains differ from strains of the Siberian subtype of TBEV that dominates in the region. The study was performed on 163 children aged 1 to 15, who received one of the vaccines according to either a conventional or rapid vaccination schedule. Immunogenicity was assessed based on the seroprotection rates and titers of virus-neutralizing antibodies. There were no significant differences in either the immunogenicity or reactogenicity of the pediatric vaccines based on strains of the Far Eastern or European subtypes of TBEV. Under both vaccination schedules, 30 days after the second injection, seroprotection rates were 100% for Tick-E-Vac and greater than 95% for FSME-IMMUN Junior, while the geometric mean titer of TBEV-neutralizing antibodies was at least 2,4 log10 (1 : 250) for either vaccine. Fourteen days after the second injection according to the rapid schedule, seroprotection rates were significantly lower, ranging from 50% to 63% regardless of the vaccine used. The observed adverse reactions were mild or moderate for both vaccines under both vaccination schedules, with total adverse event rates of less than 25%. Reactogenicity was not associated with the gender or age of the recipients. There were no statistically significant differences in the incidence of adverse reactions between the group of subjects who were baseline seronegative or seropositive. However, 14 days after the second vaccine injection according to the rapid schedule, a statistically significant difference in nAbs titers was identified between groups of children with and without reported reactions.

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
C. Q. Hoang ◽  
H. D. Nguyen ◽  
N. X. Ho ◽  
T. H. T. Vu ◽  
T. T. M. Pham ◽  
...  

Background. Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. Methods. We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. Results. The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. Conclusions. Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.


2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.


2017 ◽  
Vol 62 (1) ◽  
pp. 30-35 ◽  
Author(s):  
N. M. Pukhovskaya ◽  
O. V. Morozova ◽  
N. B. Belozerova ◽  
S. V. Bakhmetyeva ◽  
N. P. Vysochina ◽  
...  

The tick-borne encephalitis virus (TBEV) strain Lazo MP36 was isolated from the pool of mosquitoes Aedes vexans collected in Lazo region of Khabarovsk territory in August 2014. Phylogenetic analysis of the strain Lazo MP36 complete genome (GenBank accession number KT001073) revealed its correspondence to the TBEV Far Eastern subtype and differences from the following strains: 1) from ticks Ixodes persulcatus P. Schulze, 1930 [vaccine strain 205 (JX498939) and strains Khekhtzir 1230 (KF880805), Chichagovka (KP844724), Birobidzhan 1354 (KF880805) isolated in 2012-2013]; 2) from mosquitoes [strain Malyshevo (KJ744034) isolated in 1978 from Aedes vexans nipponii in Khabarovsk territory; strain Sakhalin 6-11 isolated from the pool of mosquitoes in 2011 (KF826916)]; 3) from human brain [vaccine strain Sofjin (JN229223), Glubinnoe/2004(DQ862460). Kavalerovo (DQ862460), Svetlogorie (DQ862460)]. The fusion peptide necessary for flavivirus entry to cells of the three TBEV strains isolated from mosquitoes (Lazo MP36, Malyshevo and Sakhalin 6-11) has the canonical structure 98-DRGWGNHCGLFGKGSI-113 for the tick-borne flaviviruses. Amino acid transition H104G typical for the mosquito-borne flaviviruses was not found. Structures of 5’- and 3’-untranslated (UTR) regions of the TBEV strains from mosquitoes were 85-98% homologous to the TBEV strains of all subtypes without recombination with mosquito-borne flaviviruses found in the Far East of Russia. Secondary structures of 5’- and 3'-UTR as well as cyclization sequences (CS) of types a and B are highly homologous for all TBEV isolates independently of the biological hosts and vectors. similarity of the genomes of the TBEV isolates from mosquitoes, ticks and patients as well as pathogenicity of the isolates for new-borne laboratory mice and tissue cultures might suggest a possible role of mosquitoes in the TBEV circulation in natural foci as an accidental or additional virus carrier.


Vaccine ◽  
2007 ◽  
Vol 25 (5) ◽  
pp. 895-901 ◽  
Author(s):  
Galina N. Leonova ◽  
Vladimir A. Ternovoi ◽  
Elena V. Pavlenko ◽  
Olga S. Maistrovskaya ◽  
Elena V. Protopopova ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Richard Lindqvist ◽  
Ebba Rosendal ◽  
Elvira Weber ◽  
Naveed Asghar ◽  
Sarah Schreier ◽  
...  

Abstract Background Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection range from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known; however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection. Method Mice were infected with different TBEV strains, and high virulent and low virulent TBEV strains were chosen. Sequence alignment identified differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes, mouse embryonic fibroblasts, and in vivo. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated. Results We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild-type (WT) Torö and this correlated with enhanced pathogenicity and higher levels of viral RNA in vivo. The E protein is also the major target of neutralizing antibodies; thus, genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we chose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains. Conclusions Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T, and A463S enhanced Torö infection of neurons as well as pathogenesis and viral replication in vivo; furthermore, we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.


2022 ◽  
Author(s):  
Nawal AlKaabi ◽  
Yun Kai Yang ◽  
Jing Zhang ◽  
Ke Xu ◽  
Yu Liang ◽  
...  

Background: The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. Methods: This study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged ≥18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or ≥6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate (≥4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. Findings: A total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20.47%) participants in the heterologous boost groups and 177 (19.64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89.96% - 97.52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36.80% - 81.75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21.01 - 63.85 folds from baseline to 28 days post-boosting vaccination, whereas only 4.20 - 16.78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37.91 (95%CI, 30.35-47.35), however, a significantly higher level of neutralizing antibodies with GMT 292.53 (95%CI, 222.81-384.07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. Interpretation: Our findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV.


2018 ◽  
Vol 39 (4) ◽  
pp. 191 ◽  
Author(s):  
Gerhard Dobler

Tick-borne encephalitis (TBE) is the most important tick-transmitted human viral disease in Europe and Asia with up to 10000 human cases annually. The etiologic agents of TBE are the three subtypes of tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus in the family Flaviviridae. The Far-Eastern subtype and the Siberian subtype are both mainly transmitted by Ixodes persulcatus; the European subtype is mainly transmitted by Ixodes ricinus. Besides tick bite, TBEV can be transmitted by unpasteurised milk from goat, sheep and cattle during the viremic phase of infection by the oral route of infection (alimentary form of TBE). There is no treatment for TBE available, but there are effective and well tolerated vaccines against TBE, which are recommended for people living or travelling to endemic countries with a risk of infection.


2021 ◽  
Author(s):  
Jingxin Li ◽  
Lihua Hou ◽  
Xiling Guo ◽  
Pengfei Jin ◽  
Shipo Wu ◽  
...  

Background The safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported. Methods We conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to receive a booster dose of Convidecia or CoronaVac. Participants were masked to the vaccine received but not to the three-dose or two-dose regimen. The occurrences of adverse reactions within 28 days after the vaccination were documented. The geometric mean titers of neutralizing antibodies against live SARS-CoV-2 virus were measured at 14 and 28 days after the booster vaccination. Results Between May 25 and 26, 2021, a total of 300 participants were enrolled. Participants who received a booster shot with a heterologous dose of Convidecia reported increased frequencies of solicited injection-site reactions than did those received a homogeneous dose of CoronaVac, but frequencies of systemic reactions. The adverse reactions were generally mild to moderate. The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac (197.4[167.7, 232.4] vs. 33.6[28.3, 39.8] and 54.4[37. 9, 78.0] vs. 12.8[9.3, 17.5]) at day 14 in the three- and two-dose regimen cohort, respectively. Conclusions The heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac (ClinicalTrials.gov, number NCT04892459).


2015 ◽  
Vol 20 (1) ◽  
pp. 56-64 ◽  
Author(s):  
V. V Pogodina ◽  
S. V Luchinina ◽  
O. N Stepanova ◽  
E. A Stenko ◽  
A. N Gorfinkel ◽  
...  

Lethal cases of tick-borne encephalitis in previously vaccinated patients have not been described. Modern inactivated vaccines against Tick-borne encephalitis (TBE) are high effective. The TBE cases, preference unfocal forms, are developed in persons with incomplete irregular vaccination. First case of lethal TBE after plural vaccination was described in the Kurgan region, the second case - in the Chelyabinsk region. These very rare unusual cases were studied. Being dominant the Siberian subtype of TBE virus is related with lethal TBE cases in the Chelyabinsk region. Unusual TBE case was developed in patient who had been vaccinated 8 limes with vaccines produced from strains of Far-Eastern TBE subtype («Virion», Tomsk, Chumakov institute, Moscow) and European TBE subtype (Encepur; FSME-Immun). Two years after the last vaccination a focal form of TBE was developed with lethal outcome at 9 th day. Specific antibodies IgM and IgG seroconversion were detected. The TBE virus antigen was detected in brain neurons by immunofluorescent test. Destructed neurons and gliocyles were shown by hystological study in cerebral hemispheres and cerebellum. The Purkinje cells were destructed. Possible reasons of surmounting vaccinal immunity including a genetic difference of vaccine and infection virus strains are discussed.


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