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Supplementary Information | The online version contains supplementary material available at 10.1186/s13075-023-03177-6. | PMC10577982 | ||
Keywords | PMC10577982 | |||
Background | rheumatoid arthritis, GCA, active disease, anterior ischemic optic neuropathy or stroke, RA | RHEUMATOID ARTHRITIS, POLYMYALGIA RHEUMATICA (PMR), RECRUITMENT, GIANT CELL ARTERITIS, PRIMARY SYSTEMIC VASCULITIS, GCA, CORONAVIRUS, PATHOGENESIS, COMPLICATIONS | Giant cell arteritis (GCA) is the most common primary systemic vasculitis in people above 50 years of age and is more frequently reported in Caucasians and in females [Patients with GCA may present with constitutional, polymyalgia, or cranial symptoms. Ischemic complications, such as anterior ischemic optic neuropathy ... | PMC10577982 |
Methods | PMC10577982 | |||
Study design and population | large-vessel vasculitis | PMR, GCA | This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 52-week study with a 24-week post-treatment follow-up phase (NCT03600805) (Fig. Study design. Patients were included in the study if they had a diagnosis of GCA according to the following criteria: ≥ 50 years of age; history of erythrocyte s... | PMC10577982 |
Sample size determination | Based on the results from the GiACTA trial [ | PMC10577982 | ||
Changes in conduct of study | RECRUITMENT | The study enrolled the first patient on 20 Nov 2018 but was prematurely discontinued on 21 Jul 2020 due to protracted recruitment, exacerbated by the COVID-19 pandemic; all randomized patients had to stop their study participation in 12 weeks and have a follow-up visit at 6 weeks following treatment cessation (and no l... | PMC10577982 | |
Analysis populations | The primary endpoint analysis of the patients who achieved SR at week 52 was limited to the cohort of patients who had an opportunity to complete the 52-week treatment period (i.e., week 52 analysis set). This cohort of patients was defined as the patients with a randomization date prior to 16 Oct 2019.The intent-to-tr... | PMC10577982 | ||
Statistical analyses | Due to the small sample size, only descriptive summaries by four treatment groups are presented for all baseline characteristics and endpoints. All analyses were performed with SAS Enterprise Guide Version ENGLISH 9.4. | PMC10577982 | ||
Results | PMC10577982 | |||
Patient disposition | Of 125 patients screened, a total of 83 patients were randomized and treated in the study (i.e., ITT population): 27 patients in the SAR200 + 26W taper group, 14 patients in the SAR150 + 26W taper group, 28 patients in the PBO + 52W taper group, and 14 patients in the PBO + 26W taper group (Fig. Patient disposition. Of... | PMC10577982 | ||
Outcome assessments | PMC10577982 | |||
Secondary efficacy endpoints | PMC10577982 | |||
Pharmacodynamics | From week 12 through week 52, CRP levels in the sarilumab groups were maintained at < 10 mg/L and were lower than that observed in the PBO groups (Additional file Mean changes in IL-6 and sIL-6R levels over time from baseline through week 52 are depicted in Fig. Change from baseline in IL-6 and sIL-6R levels during the... | PMC10577982 | ||
Pharmacokinetics | The PK analysis set comprised 26 patients in the SAR200 + 26W taper group and 14 patients in the SAR150 + 26W taper group. All pre-dose concentrations of functional sarilumab in serum at week 0 were below the lower limit of quantification (312.5 ng/mL). After multiple SC administrations of sarilumab, the observed troug... | PMC10577982 | ||
Discussion | ’ disease, neutropenia, retinal artery occlusion, PD, RA | NEUTROPENIA, UNILATERAL BLINDNESS, DISEASE, RECRUITMENT, RETINAL ARTERY OCCLUSION, REMISSION, GCA, INFLAMMATORY RESPONSE | This study was designed to evaluate the efficacy and safety of sarilumab in patients with GCA; however, it was prematurely terminated, resulting in low enrollment and a limited dataset for statistical analyses. Due to the decision to discontinue all patients from the study, the interpretation of the study results was s... | PMC10577982 |
Conclusions | RECRUITMENT, GCA | The planned recruitment of this study was not achieved, as it was stopped early by the sponsor due to slow recruitment and the COVID-19 pandemic. Therefore, it is difficult to draw clear conclusions regarding the efficacy of sarilumab in GCA. | PMC10577982 | |
Acknowledgements | Medical writing support for this manuscript was provided by Vasudha Chachra, MPharm of Sanofi. | PMC10577982 | ||
Authors’ contributions | RS | WAS, BD, JS, AG, SHU, SLM, MAG, RS, KJW, PMV, MCN, BA, YL, FB, and JHS substantially contributed to the conception or design of the work. YX was involved in data analysis. All authors were involved in the interpretation of data for the work, reviewed the manuscript for important intellectual content, and approved the f... | PMC10577982 | |
Authors’ information | Angeliki Giannelou’s Affiliation at the time of the conduct of study. | PMC10577982 | ||
Funding | This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. | PMC10577982 | ||
Availability of data and materials | Qualified researchers may request access to patient-level data and related documents (including, e.g., the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications). Patient-level data will be anonymized, and study documents will be redacte... | PMC10577982 | ||
Declarations | PMC10577982 | |||
Ethics approval and consent to participate | The study was conducted according to the principles defined in the Declaration of Helsinki and Good Clinical Practices. All participating investigators obtained full ethics or institutional review board approval according to their local regulations. The Ethik-Kommission des Landes Berlin, Landesamt für Gesundheit und S... | PMC10577982 | ||
Consent for publication | Not applicable. | PMC10577982 | ||
Competing interests | RS, MCN | CORBUS | WAS: Received consulting fees and grants from AbbVie, GSK, Novartis, Roche, and Sanofi; speakers bureau for AbbVie, Chugai, GSK, Novartis, Roche, and Sanofi; has been an investigator on clinical trials for AbbVie, GSK, Novartis, and Sanofi. BD: Consultant for Sanofi and Roche Chugai; speakers bureau for Roche Chugai an... | PMC10577982 |
References | PMC10577982 | |||
Introduction | Postural orientation requires the integration of vestibular, visual, and somatosensory information. Perception of the body in space also enables postural control and body movements [The effect of NMV on postural orientation differs during and after stimulation [The subjective straight ahead (SSA), a measurement that in... | PMC9879387 | ||
Materials and methods | PMC9879387 | |||
Study design and participants | RECRUITMENT | This was an interventional study with a cross-over design. Approval was obtained from the Research Safety Ethics Review Committee of the Tokyo Metropolitan University Arakawa Campus (approval number: 20021) and the Tokyo Metropolitan Rehabilitation Hospital (approval number: 2021–10). All participants were informed, bo... | PMC9879387 | |
Vibration settings | Vibratory stimulation was performed using a speaker-type stimulator [ | PMC9879387 | ||
Speaker-type stimulator. | PMC9879387 | |||
Location of vibratory stimulators. | The vibratory stimulators are fixed in two circular positions in the sitting position. | PMC9879387 | ||
Outcome measures | Standing COP was measured using a COP platform (SR Vision by Sumitomo Riko Co. Ltd, Nagoya, Japan) to assess standing postural orientation. The frequency of signals was recorded at a sampling rate of 20 Hz to generate the COP data, which is valid and reliable for quantifying standing balance [To assess spatial percepti... | PMC9879387 | ||
Procedures | The participants sat on a stable seat 40-cm high with both feet on the COP platform. Measurements were performed before and after stimulation. First, SSA was measured during the sitting position. Next, the participants stood up with their eyes open, and standing COP was measured with eyes closed for 30 s, and then with... | PMC9879387 | ||
Statistical analysis | Measurements of COP and SSA values were subtracted before and after each condition for standardized variation. Statistical analysis was conducted using one-way analysis of variance with repeated measures or Greenhouse–Geisser correction [The sample size was calculated using G*Power version 3.1 [ | PMC9879387 | ||
Results | The study included 24 participants (all right-handed; 12 males; 25.7±3.7 years; WBL with closed eyes 50.2±2.3%; WBL with open eyes: 50.4±2.8%), and they performed all four conditions, and a total of 96 trials was conducted.A one-way analysis of variance with repeated measures showed that the left lower limb loading rat... | PMC9879387 | ||
Differences in the mean position of COP before and after vibration (n = 24). | POSITIVE | Error bars indicate the standard error. A. The results of Dunnett’s test on the mean position of ML-COP with closed eyes. Positive values indicate a rightward deviation, whereas negative values indicate a leftward deviation on the mediolateral plane. B. The results of Dunnett’s test on the mean position of AP-COP with ... | PMC9879387 | |
The results of one-way analysis of variance with repeated measures. | WBL, percentage of weight on the left limb; ML, mediolateral; AP, anteroposterior; CE, closed eyes; OE, open eyes: COP, center of pressure; SSA, subjective straight aheada, p < 0.05b, Greenhouse–Geisser p < 0.05. | PMC9879387 | ||
Discussion | visual illusions, closed-eye, Proprioceptive sensations | This study aimed to clarify the effects of NMV on standing postural orientation and spatial perception in healthy participants, depending on differences in stimulation duration and simultaneous stimulation of trunk muscles. The results of this study showed that compared to the control condition, ML-COP was biased to th... | PMC9879387 | |
1. Introduction | dysbiosis, asthma/allergic disease | LATE PREGNANCY, ASTHMA, VITAMIN D DEFICIENCY, REGRESSIONS | Shifts in the maternal gut microbiome and vitamin D deficiency during pregnancy have been associated, separately, with health problems for both the mother and the child. Yet, they have rarely been studied simultaneously. Here, we analyzed the gut microbiome (from stool samples obtained in late pregnancy) and vitamin D ... | PMC10181263 |
2. Materials and Methods | PMC10181263 | |||
2.1. Vitamin D Antenatal Asthma Reduction Trial (VDAART) | asthma | ASTHMA | VDAART was a randomized controlled trial of Vitamin D supplementation during pregnancy to prevent asthma in offspring conducted in the United States (St. Louis, Boston, and San Diego; NCT00920621). Eight hundred and seventy women were enrolled at 10–18 weeks of gestation and randomized to receive either a high dose of ... | PMC10181263 |
2.2. Stool Sample Collection and Processing | During the third trimester of pregnancy (weeks 32–38 gestation), 120 participants of the VDAART trial provided a stool sample. Subjects were asked to collect a 0.5 teaspoon-sized sample 1 to 2 days before a study visit and store the sample in a home freezer before transport with a freezer pack to the study site. Stool ... | PMC10181263 | ||
2.3. Blood Sample Collection and Processing | LATE PREGNANCIES | Maternal blood samples were collected at two time points: at enrollment at 10–18 weeks of gestation and at 32–38 weeks of gestation. The serum 25-hydroxyvitamin D 25(OH)D level (termed as the vitamin D level hereafter) was measured in both samples using the DiaSorin LIAISON method (a chemiluminescence assay) at the Cha... | PMC10181263 | |
2.4. Serum Vitamin D Level | For the 114 women with baseline and final measurements ( | PMC10181263 | ||
2.5. Mothers’ Characteristics | asthma | HAY FEVER, ASTHMA | The stool and blood samples were collected at three different sites: Boston, MA; San Diego, CA; and St. Louis, MO. The available subjects’ characteristics from the initial enrollment questionnaire are the mothers’ age, race, education, household income, and history of asthma and hay fever. Mothers were categorized into... | PMC10181263 |
2.6. Statistical Analyses | For the statistical analyses, we measured the vitamin D status in three different ways: baseline vitamin D level (measured at enrollment), randomized treatment assignment (treatment or placebo supplementation), and vitamin D level change between the baseline and final measurements (high or low change). Unless specifica... | PMC10181263 | ||
2.6.1. Alpha Diversity | Alpha diversity measures are estimates of an individual sample’s taxonomic diversity. We computed the observed richness, Shannon, and Simpson indices using the Phyloseq package in R [ | PMC10181263 | ||
2.6.2. Beta Diversity | Beta diversity measures quantify the dissimilarity in taxonomic composition between two samples. We computed the following measures: Bray–Curtis dissimilarity, Jaccard distance, Unifrac distance, and Weighted-Unifrac distance using the Phyloseq package in R. We used the adonis2 algorithm in the R package vegan [ | PMC10181263 | ||
2.6.3. Abundance Association Analysis | To ensure robustness of the identified associations, we used two different methods and their corresponding R packages, which look for associations between the subject variables and the abundance of specific taxa: ANCOM-BC [ | PMC10181263 | ||
3. Results | PMC10181263 | |||
3.2. Microbiome Composition Is Associated with Baseline Vitamin D Level | We found a small but not statistically significant positive correlation between the baseline vitamin D level and gut microbiome richness or for the three alpha diversity indices analyzed ( | PMC10181263 | ||
3.3. Gut Microbiome Is Robust to Vitamin D Supplementation during Pregnancy | In an intention-to-treat analysis, we found no significant associations between the participants’ treatment assignment and any of the alpha diversity indices that we calculated ( | PMC10181263 | ||
3.4. Change in Vitamin D Level Does Not Impact Microbiome Diversity | Comparing participants by the change in their vitamin D level allows for an assessment of the impact of vitamin D over a relatively short period (between weeks 10–18 and weeks 32–38 of pregnancy) on the microbiome and accounts for potential lack of adherence to the vitamin D supplementation treatment assignment. All th... | PMC10181263 | ||
3.5. Desulfovibrio Is Enriched in Pregnant Women with Low Change of Vitamin D Level | Next, we looked at differentially abundant taxa between the change groups at the genus level. We found that two genera were enriched in the low change group (Interestingly, we found that the presence of | PMC10181263 | ||
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10181263 | ||
Author Contributions | Conceptualization, S.T.W., K.L.-S. and Y.-Y.L.; methodology, K.L.-S., Y.-Y.L. and A.A.; software, A.A.; validation, K.L.-S.; formal analysis, A.A.; investigation, A.A.; data curation and essential databases, D.R.G. and A.A.L.; writing—original draft preparation, A.A.; writing—review and editing, all authors; visualizat... | PMC10181263 | ||
Institutional Review Board Statement | The study protocol was approved by the institutional review boards at each participating institution and at Brigham and Women’s Hospital. The study was conducted in accordance with the Declaration of Helsinki. | PMC10181263 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10181263 | ||
Data Availability Statement | Microbiome sequencing data from VDAART are part of the ECHO consortium, and ECHO consortium members can obtain the data directly from the ECHO DCC or for those not part of ECHO directly from the authors. All other relevant data are available from the authors upon reasonable requests. | PMC10181263 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10181263 | ||
References | Vitamin D status was measured in three different ways: baseline vitamin D level (serum 25-hydroxyvitamin D 25(OH)D (ng/mL) measured in a blood sample at enrollment), treatment assignment (treatment or placebo vitamin D supplementation), and vitamin D level change over the trial period (high change or an increase of at ... | PMC10181263 | ||
Background | Flavivirus infections, TBEV, tick-borne encephalitis, YFV, yellow fever | VIRUS, JAPANESE ENCEPHALITIS, TICK-BORNE ENCEPHALITIS, YELLOW FEVER, FLAVIVIRUS INFECTION | The authors have declared that no competing interests exist.‡ These authors are joint senior authors on this work.Flavivirus infections pose a significant global health burden underscoring the need for the development of safe and effective vaccination strategies. Available flavivirus vaccines are from time to time conc... | PMC9946270 |
Methods and findings | YFV, TBEV | ADVERSE EVENTS, ADVERSE EFFECTS, ADVERSE EVENT | Following screening, healthy study participants were enrolled into different cohorts receiving either TBEV and YFV vaccines, JEV and YFV vaccines, or in control groups receiving only the TBEV, JEV, or YFV vaccine. Concomitant delivery was given in the same or different upper arms for comparison in the co-vaccination co... | PMC9946270 |
Conclusions | YFV, TBEV | ADVERSE EVENTS | Inactivated TBEV or JEV vaccines can be co-administered with the live attenuated YFV vaccine without an increased risk of adverse events and without reduced development of nAbs to the respective viruses. The vaccines can be delivered in the same upper arm without negative outcome. In a broader perspective, the results ... | PMC9946270 |
Trial registration | Eudra | PMC9946270 | ||
Author summary | PMC9946270 | |||
Why was this study done? | YFV, yellow fever, TBEV | VIRUS, JAPANESE ENCEPHALITIS, TICK-BORNE ENCEPHALITIS, YELLOW FEVER, FLAVIVIRUS INFECTION | Flavivirus infections pose a significant global health burden, underscoring the need for the development of safe and effective vaccination strategiesCo-administration of different vaccines, including flavivirus vaccines, saves time and visits to health care units and vaccine clinics. It serves to provide protection aga... | PMC9946270 |
What did the researchers find? | ADVERSE EVENT | Adverse events, neutralizing antibodies (nAbs) and other related immunological parameters were not detrimentally affected by concomitant delivery of the vaccinesConcomitant vaccination in the same versus different upper arms of study participants did not significantly affect safety or immunogenicity outcomes | PMC9946270 | |
What do these findings mean? | YFV, TBEV | ADVERSE EVENTS | Co-administration of YFV vaccine and TBEV or JEV vaccines is feasible without increased risk of adverse events or reduced development of nAbs against the respective viruses. | PMC9946270 |
Data Availability | All relevant data are within the manuscript and its | PMC9946270 | ||
Introduction | YFV, JEV infections, TBEV, Yellow fever | VIRUS, YELLOW FEVER, JAPANESE ENCEPHALITIS, TICK-BORNE ENCEPHALITIS, BLOOD | Yellow fever virus (YFV), tick-borne encephalitis virus (TBEV), and Japanese encephalitis virus (JEV) all belong to the The vaccine regimen and outcome of vaccinations against YFV, TBEV, and JEV infections differ significantly. After a single dose, the live attenuated YFV 17D vaccine provides at least 10 years, and pos... | PMC9946270 |
Methods | PMC9946270 | |||
Ethical and regulatory approval | The study was approved by the Stockholm Local Regional Ethical Committee (2017/1433-31/1) and the Swedish Medical Products Agency (5.1-2017-52376). It is registered in the European database (Eudra CT 2017-002137-32). All study volunteers signed informed consent documents in line with the ethical approval and clinical t... | PMC9946270 | ||
Clinical trial design | non-Pharma | An open label, non-randomized academic (non-Pharma sponsored) clinical trial was conducted in order to assess safety and immunological responses of concomitant vaccination with three currently licensed flavivirus vaccines. The trial was conducted at the Karolinska University Hospital, Stockholm, Sweden. An independent ... | PMC9946270 | |
Vaccines | YFV | The following vaccines were used in the trial: Stamaril (Sanofi), live, attenuated YFV 17D strain produced in pathogen-free chick embryo cells, 0.5 ml, not less than 1,000 IU. The vaccine was provided in freeze dried powder form and reconstituted with provided saline solution and was administered subcutaneously. IXIARO... | PMC9946270 | |
Study participants and cohorts | YFV, TBEV | The study was initially designed to include a total of 140 healthy volunteers. Forty study participants were to receive both TBEV and YFV vaccines (cohort A). Twenty of these participants were to receive the vaccines in different upper arms (sub-cohort A1) and the other 20 in the same upper arm (sub-cohort A2). The nex... | PMC9946270 | |
Clinical trial layout for study participants and vaccination strategy with sampling timeline. | ( | PMC9946270 | ||
Procedures | BLOOD | Vaccinations were given in accordance with the clinical trial protocol and good clinical practice (GCP), with intervals for primary vaccinations as recommended in FASS (Pharmaceutical Specialties in Sweden): FSME IMMUN, three doses 0-, 1- and 5-month intervals; IXIARO, two doses, 0- and 1-month interval; Stamaril, one ... | PMC9946270 | |
Safety assessment | ADVERSE EVENTS, ADVERSE EVENT, EVENTS | Results from physical examination, including vital signs and body temperature, pulse, and blood pressure was recorded at each time-point for vaccination. Adverse events (AEs) following vaccinations were self-reported by the study participants at each study visit. Briefly, upon each 30 min visit (up to 10 visits per stu... | PMC9946270 | |
Determination of YFV RNA in serum | YFV | YFV-specific real-time PCR was used to determine the viral RNA in serum of study participants. RNA was isolated from 150 μL of serum using a NucleoSpin RNA Virus Kit (Machery-Nagel). One step real-time PCR was performed using TaqMan Fast Virus 1-Step Master Mix (Applied Biosystems), a FAM-TAMRA-labeled probe and primer... | PMC9946270 | |
Clinical chemistry | C-reactive protein (CRP), albumin (ALB), creatinine, bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were analyzed at the Karolinska University Hospital accredited clinical chemistry laboratory at the first three time-points (days ... | PMC9946270 | ||
Absolute cell counts | LYSING | Absolute numbers of cells expressing CD45, CD3, CD4, and CD8 in peripheral blood were measured using BD TruCount tubes (BD Biosciences) according to the manufacturer’s instructions. Briefly, 50 μL of anticoagulated blood was added to TruCount tubes within three hours after extraction and thereafter fluorescently staine... | PMC9946270 | |
Multiplex measurement of cytokine secretion | GM-CSF, IFN-ɣ, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-ɑ2, MIP-1β, IL-12, IL-15 and IL-18 were measured in serum, diluted 1:4, from the first four time-points (days 0, 7, 14, and 30) from each study participant using a pre-designed 8-plex assay with a custom-designed 5 single-plex assay Bio-Plex Pro Human Cytokine Assa... | PMC9946270 | ||
Antibody analyses | YFV, TBEV | VIRUS | Assessment of virus-specific IgG levels and nAbs against TBEV, JEV and/or YFV was performed on day 0, day 30, and at the final time-point of the clinical trial (day 210 for cohort A and cohort C, day 60 for B, D, and E). TBEV-specific IgG antibodies were assessed using an anti-TBE virus ELISA “Vienna” (IgG) kit (Euroim... | PMC9946270 |
Flow cytometry | APC | Freshly isolated PBMCs were used for phenotypical analysis using the following antibodies: Live/Dead cell marker Near IR (Life Sciences), anti-CD19 (clone SIJ25C1) BUV 395, anti-CD4 (clone SK3) BUV 737, anti-CD16 (clone 3GB) Pacific Blue, anti-CD14 (clone MφP9) AmCyan, anti-Ki67 (clone B56) AF700 (BD Biosciences), anti... | PMC9946270 | |
CXCL13 ELISA | Undiluted serum was thawed at room temperature and analyzed using a Quantikine Human CXCL13/BLC/BCA-1 ELISA (R&D Systems) according to the manufacturer’s instructions. Limit of detection of the assay ranged between 7.8 and 500 pg/mL. | PMC9946270 | ||
Statistics | Statistical analyses were performed using GraphPad Prism (GraphPad Software). Data sets were analyzed using non-parametric Wilcoxon matched-pairs signed rank test, Kruskal-Wallis, Friedman tests, or Fisher’s exact test. Dunn’s multiple comparisons test was used to correct for multiple comparisons where applicable. Hand... | PMC9946270 | ||
Results | PMC9946270 | |||
Study participants and vaccination schedule | 140 study participants were planned for the present clinical trial. Over the course of 17 months, 161 volunteers were screened, 145 of whom were found to be eligible for the clinical trial and enrolled into one of the seven cohorts (A1, A2, B1, B2, C, D, and E). All but six study participants completed the trial, leavi... | PMC9946270 | ||
Cohort characteristics. | PMC9946270 | |||
Adverse events | 69.8% of the 139 included study participants reported one or more AEs during the course of the clinical trial ( | PMC9946270 | ||
Summary of registered adverse events over the entire study period. | pneumonitis, hip dysplasia, depression, TBEV | PNEUMONITIS | Briefly, cohorts A1, A2 and C, all of which received TBEV vaccinations, had a greater number of total registered AEs compared to the other cohorts, ascribed to multiple (n = 3) TBEV vaccinations. Cohorts B1, B2, and D, all of which received JEV vaccinations, had greater number of total registered AEs compared to the E ... | PMC9946270 |
Viral RNA levels, clinical chemistry, and immunology | YFV, infection | INFECTION, VIRUS | The YFV vaccine causes a mild infection, often with detectable virus in circulation. As a safety-related assessment, we measured serum YFV NS5-RNA levels in all cohorts vaccinated with the YFV vaccine in order to assess if concomitant vaccination had any effects on YFV viral replication. Across all study cohorts, most ... | PMC9946270 |
Virus specific IgG levels | TBEV | VIRUS | As part of the primary endpoint, TBEV and JEV specific IgG levels were measured before vaccination and at days 30 (30 days after dose 1) and 210 (30 days after dose 3) for the TBEV vaccine cohorts, and at days 30 (30 days after dose 1) and 60 (30 days after dose 2) for the JEV vaccine cohorts. Study participants with d... | PMC9946270 |
Virus neutralization | YFV, TBEV | Apart from the assessment of antigen-binding IgG responses, rapid fluorescence focus inhibition tests (RFFIT) were performed to measure nAb titers against TBEV, JEV, and YFV to compare the effect of concomitant vaccinations with respective single vaccination outcomes. All study participants were screened at day 0 for n... | PMC9946270 | |
Activation of B cells, T cells and NK cells | In addition to the virus-specific binding IgG antibody responses and nAbs we, we expanded the analyses in exploratory studies to investigate specific cellular responses following vaccination of the different cohorts. Freshly isolated PBMCs from each time-point were used to assess the effects of concomitant vaccinations... | PMC9946270 | ||
Germinal center activation and plasmablast responses | YFV | The observed activation of lymphocyte subsets indicates induction of innate and adaptive immune responses, likely linked to the development of protective immunity (nAbs). We therefore further explored parameters related to induction of humoral immunity such as germinal center activity and plasmablast expansion followin... | PMC9946270 | |
Discussion | YFV, TBEV | COLD SYMPTOMS | Here, we report the results of an open label, non-randomized, academic clinical trial assessing the safety and immunogenicity upon concomitant vaccination with different commonly used flavivirus vaccines. Healthy study participants were enrolled into cohorts receiving vaccines against TBEV and YFV in different or the s... | PMC9946270 |
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