Geometric Mean Concentrations Research Articles

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone

This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. For the French translation of the abstract see Supplementary Materials section.

Biomonitoring of exposure to multiple metal components in urine, hair and nails of apprentice welders performing shielded metal arc welding (SMAW)

Welding fumes are associated with various diseases. Increased air levels of metals were reported during welding. However, few multielement biomonitoring studies were conducted to assess the actual dose of metal components absorbed in apprentice welders in a learning environment. This research aimed to establish the nature and level of exposure to welding fumes and their metallic components in apprentice welders performing ‘Shielded Metal Arc Welding’ (SMAW), based on multi-element and multi-matrix analyses. A total of 86 apprentice welders were recruited in three different schools in Montreal, Québec, Canada. Twenty-one elements were measured in urine, hair, fingernail, and toenail samples collected at the beginning of the program and at the end of SMAW practical training. Concentrations of welding fumes and 12 metals were also determined in personal respirable air samples collected over a typical workday in a subgroup of 19 apprentices. Levels of manganese (Mn), iron (Fe) and nickel (Ni) in urine and Mn in hair were higher in samples taken at the end of the SMAW module compared to the beginning of training, while there was no significant difference for the other elements or for nail concentrations. Geometric mean concentrations [5th-95th percentiles] reached 0.31 [0.032–2.84], 9.4 [3.1–51] and 0.87 [0.35–3.1] μg/g creat. in post-shift urine, respectively, for Mn, Fe and Ni, and 0.37 [0.46–6.4] μg Mn/g hair at the end of SWAW. Median concentrations [5th-95th percentiles] were 29 [4.6–1200], 120 [27–3100] and 0.31 [<LOQ-0.92] μg/m3 for Mn, Fe and Ni, respectively. The work showed that even short-term welding fume exposure in controlled environments, as observed in apprentice welders after SMAW process, increases internal exposure to metals. It also confirmed the interest of measurements in multiple matrices to assess internal metal exposure. The follow-up of apprentices during standard curriculum will allow to assess more long-term internal exposure due to other welding processes.

Safety and immunogenicity of SIIPL Tdap, a new tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, in healthy subjects 4–65 years of age: A Phase II/III randomized, observer-blinded, active controlled, multicenter clinical study in Germany

BackgroundThis study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). MethodsThe Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. ResultsAt Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. ConclusionsBooster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated.EudraCT number: 2019-002706-46.

Use of silicone wristbands to measure firefighters’ exposures to polycyclic aromatic hydrocarbons (PAHs) during live fire training

Firefighters experience exposures to carcinogenic and mutagenic substances, including polycyclic aromatic hydrocarbons (PAHs). Silicone wristbands (SWBs) have been used as passive samplers to assess firefighters' exposures over the course of a shift but their utility in measuring short term exposures, source of exposure, and correlations with other measurements of exposure have not yet been investigated. In this study, SWBs were used to measure the concentrations of 16 priority PAHs inside and outside of firefighters’ personal protective equipment (PPE) while firefighting. SWBs were placed on the wrist and jacket of 20 firefighters conducting live fire training. Correlations were made with matching data from a sister project that measured urinary concentrations of PAH metabolites and PAH concentrations from personal air samples from the same participants. Naphthalene, acenaphthylene and phenanthrene had the highest geometric mean concentrations in both jacket and wrist SWB, with 1040, 320, 180 ng/g SWB for jacket and 55.0, 4.9, and 6.0 ng/g SWB for wrist, respectively. Ratios of concentrations between the jacket and wrist SWBs were calculated as worker protection factors (WPFs) and averaged 40.1 for total PAHs and ranged from 2.8 to 214 for individual PAHs, similar to previous studies. Several significant correlations were observed between PAHs in jacket SWBs and air samples (e.g., total and low molecular weight PAHs, r = 0.55 and 0.59, p < 0.05, respectively). A few correlations were found between PAHs from SWBs worn on the wrist and jacket, and urinary concentrations of PAH metabolites and PAH concentrations in air samples. The ability of the SWBs to accurately capture exposures to various PAHs was likely influenced by short sampling time, high temperatures, and high turbulence. Future work should further examine the limitations of SWBs for PAH exposures in firefighting, and other extreme environments.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BackgroundIn 2019, the 3 + 1 schedule for children’s vaccination (2–4–6–18 months old) was changed for a reduced 2 + 1 schedule (2–4–12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. MethodsWe conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children’s blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. ResultsA total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65–0.90), 0.66 (0.55–0.79), 0.72 (0.52–0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. ConclusionInfant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children’s protection.

Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial.

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults

BackgroundPlasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. MethodsIn this study, a total of 2607 subjects aged 18–79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. ResultsThe geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high‐density lipoprotein cholesterol (HDL-C) levels increased. ConclusionsOur findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Association of non-daily hookah tobacco smoking and cardiovascular disease-related exposure biomarkers among U.S. users: The Population Assessment of Tobacco and Health Study

Hookah smoking has grown to become a global tobacco epidemic. While cigarette smoking is a well-established cardiovascular disease (CVD) risk factor, the CVD risks of hookah smoking are unknown, particularly among regular U.S. adult hookah users who are predominantly non-daily users. Herein, we examined the association between hookah smoking and biomarkers of CVD risk among regular exclusive hookah smokers (n = 75), compared to regular exclusive cigarette smokers (n = 1773), dual hookah and cigarette smokers (n = 43) and never tobacco users (n = 757), using data from a nationally representative sample of adults from the Population Assessment of Tobacco and Health Study (2013–2014). Whereas 84% of cigarette smokers reported daily use, only 8% of hookahsmokers reported daily use, with more than a third reporting monthly use. Adjusting for age and sex and as compared to exclusive cigarette smokers, exclusive hookah smokers had significantly lower geometric mean concentrations in serum sICAM-1 and urinary F2-isoprostane (p < 0.05). Although not statistically significant, a signal of increased oxidative stress was observed among hookah smokers as compared to never tobacco users (urinary F2-isoprostane). CVD-related harm biomarkers appear to be lower among hookah smokers than cigarette smokers. These findings represent patterns of hookah smoking predominantly shared among adult U.S. users who report non-daily occasional use and do not reflect solitary, daily use as is common in the Middle East. Future studies with longer exposure and longitudinal hookah use are warranted to explore the association between hookah smoking and CVD risk.

Exposure to Bisphenol A and Its Analogs among Thai School-Age Children.

Bisphenol F (BPF) and bisphenol S (BPS) have become popular substitutes for bisphenol A (BPA) in the plastic industry due to concerns over BPA's adverse effects. However, there is limited information on children's exposure to these chemicals. This study aims to assess the extent of BPA, BPF, and BPS exposure and determine factors that influence such exposure. A group of Thai children (age 6-13 years, N = 358) were recruited between October 2019 and 2020. Two first-morning voids were collected one week apart. Demographic and exposure-related information was gathered. Urinary concentrations of bisphenols were analyzed by liquid chromatography and tandem mass spectrometry. Correlation between bisphenol concentrations with age, body weight, and sources of bisphenol exposure, was determined using generalized estimating equations with linear model. BPA, BPF, and BPS were detected at 79.6%, 31.0%, and 16.8%, with geometric mean (GM) concentrations of 1.41, 0.013, and 0.014 ng/mL, respectively. Younger children aged <10 years exhibited 1.3-1.6 times higher GM levels of all bisphenols compared to older children. Exposure to food stored in plastic containers was associated with higher levels of BPF and BPS. In conclusion, BPA was the most frequently detected bisphenol in urine samples from Thai children, followed by BPF and BPS.

Explore the optimal timing for administering the second dose of the varicella vaccine in China.

The prevalence of varicella in China has been increasing annually, with a relatively high incidence rate of breakthrough cases. Administering two doses of the varicella vaccine (Varv) proves to be the most effective measure. The objective of this study is to assess the immunogenicity of two doses of the Varv at varying intervals and explore the optimal timing for administering the second dose of the Varv. Utilizing a prospective cohort study design, the quantification of varicella immunoglobulin G (IgG) antibodies' geometric mean concentrations (GMC) is conducted through glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A total of 903 infants were included in the per-protocol population. After completing the first dose of the Varv, the GMC of antibody after 1 month (Group A) was 463.8 (447.6-480.1) mIU/mL. There was a statistically significant difference in GMC and seroconversion rates among the groups (B/C/D) that received the second dose of the Varv (p < 0.05). Multiple comparisons revealed that the group with a 3-year interval between the two vaccine doses had a higher GMC of 665.2 (622.6-707.8) mIU/mL compared to the group with a 1-year interval of 611.1 (577.1-645.3) mIU/mL and the group with a 5-year interval of 564.7 (540.1-589.4) mIU/mL. To effectively prevent and control the varicella epidemic in Jiangsu Province, two dose Varvvaccination is recommended, the optimal time point for the second dose Varvis 3 years after the first vaccination.

Safety and immunogenicity of a new formulation of a pentavalent DTwP-HepB-Hib vaccine in healthy Indian infants-A randomized study.

Pentavalent vaccines (DTP-HepB-Hib) have been introduced in many countries in their routine public immunization programmes to protect against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (Hep B) and Hemophilus influenzae type b (Hib) diseases. This study compared the safety and immunogenicity of a new formulation of a whole-cell Bordetella pertussis (wP) based pentavalent vaccine (DTwP-HepB-Hib). The new formulation was developed using well-characterized hepatitis B and pertussis whole cell vaccine components. This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6-8, 10-12 and 14-16 weeks of age. The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89-1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73-1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. Clinical Trials Registry India number: CTRI/2018/12/016692.

Vaccine-induced and hybrid immunity to SARS-CoV-2 after three or four doses of BNT162b2 - results from 22 months follow-up of a healthcare workers cohort, Israel, 2020-2022

ObjectivesSARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected. MethodsWe periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance. ResultsAmong the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two. ConclusionThree BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.

Safety and Immunogenicity of V114 in Preterm Infants: A Pooled Analysis of Four Phase Three Studies.

Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in PCV13 plus 2 unique serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 pediatric phase 3 studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Healthy preterm infants were randomized 1:1 to receive V114/PCV13 in the 4 studies. Safety was evaluated as the proportion of participants with adverse events (AEs) following receipt of PCV. Serotype-specific antipneumococcal immunoglobulin G (IgG) geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were measured at 30 days postdose 3, pretoddler dose and 30 days postdose 4. V114 and PCV13 were administered to 174 and 180 participants, respectively. Mean gestational age was 35.4 weeks (range: 27 - <37 weeks). Proportions of participants with AEs were comparable between vaccination groups; most AEs experienced were of short duration (≤3 days) and mild-to-moderate intensity. V114-elicited IgG geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days postdose 3 and postdose 4. In preterm infants, V114 was well tolerated and induced comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to serotypes 22F and 33F. Results support the use of V114 in preterm infants.

Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial

ObjectivesWe explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel. MethodsVolunteers aged ≥18 years (n = 305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13) + HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28 ± 3 days after vaccination. Adverse events (AEs) were recorded over 4 weeks. ResultsAfter vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42–44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01–96.72 mIU/mL), p < 0.001. Anti-HAV ≥10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: ≥one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data. DiscussionCoadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA.

Safety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults

Data on the safety and immunity of a heterologous booster (fourth dose) after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults are limited. We evaluate the safety and immunogenicity of Ad5-nCoV in a randomized, double-blind, parallel-controlled phase 4 clinical trial in Zhejiang, China (NCT05373030). Participants aged 18–80 years (100 per group), administered three doses of inactivated SARS-CoV-2 vaccine ≥6 months earlier, are enrolled and randomized 1:1 into two groups, which are administered intramuscular Ad5-nCoV or inactivated SARS-CoV-2 vaccine (CoronaVac or Covilo). All observed adverse reactions are predictable and manageable. Ad5-nCoV elicits significantly higher RBD-specific IgG levels, with a geometric mean concentration of 2924.0 on day 14 post-booster, 7.8-fold that of the inactivated vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 show a similar pattern, with geometric mean titers of 228.9 in Ad5-nCoV group and 65.5 in inactivated vaccine group. Ad5-nCoV booster maintains high antibody levels on day 90, with seroconversion of 71.4%, while that of inactivated vaccine is 5.2%, almost pre-booster levels. A fourth Ad5-nCoV vaccination following three-doses of inactivated SARS-CoV-2 vaccine is immunogenic, tolerable, and more efficient than inactivated SARS-CoV-2 vaccine. Ad5-nCoV elicits a stronger humoral response against Omicron BA.4/5 and maintains antibody levels for longer than homologous boosting.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study

Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

The Decay of Pertussis Antibodies in Children Aged 0-14 Years in Jiangsu Province, China.

The purpose of this study was to investigate possible influencing factors based on the distribution of the pertussis toxin (PT) and filamentous hemagglutinin (FHA) antibody levels in 0-14-year-old children in Jiangsu Province, China, and to analyze changes in IgG antibody levels after pertussis vaccination in children over time via a restricted cubic spline (RCS)-fitted binary logistic regression model. We collected surveillance data on pertussis through the National Notifiable Disease Reporting System (NNDRS). Serum samples were collected, and PT IgG/FHA IgG antibody levels were determined via an enzyme-linked immunosorbent assay (ELISA). A binary logistic regression model was fitted with an RCS. Peak incidence occurred in children aged 0-1 years from 2007 to 2022, and a second peak emerged in children aged 5 years and older from 2018 onwards which shifted towards older age groups. The geometric mean concentrations (GMC) of the anti-PT IgG antibody and anti-FHA IgG antibody in 1129 patients were 15.13 (13.49-16.76) IU/mL and 22.99 (21.17-24.81) IU/mL, respectively. The seropositivity rates of the anti-PT IgG and anti-FHA IgG antibodies in the group receiving a full vaccination course (four doses) were significantly higher than those of other groups (24.6% vs. 43.3%). The RCS fitting model showed a non-linear relationship between the duration after immunization and the odds ratio (OR) of having PT-IgG and FHA-IgG antibody concentrations ≥20 IU/mL in children with documented immunization histories (1-4 doses) (Poverall < 0. 001; Pnonlinear ≤ 0.001). The children with histories of immunization demonstrated antibody levels that decreased to very low levels around 17 months after the last dose of the vaccine. Therefore, it is recommended that pertussis-containing vaccines be administered as booster immunizations for older children.

The Effect of Previous Exposure to Malaria Infection and Clinical Malaria Episodes on the Immune Response to the Two-Dose Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen.

We assessed whether the immunogenicity of the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen with a 56-day interval between doses was affected by exposure to malaria before dose 1 vaccination and by clinical episodes of malaria in the period immediately after dose 1 and after dose 2 vaccinations. Previous malaria exposure in participants in an Ebola vaccine trial in Sierra Leone (ClinicalTrials.gov: NCT02509494) was classified as low, intermediate, and high according to their antibody responses to a panel of Plasmodium falciparum antigens detected using a Luminex MAGPIX platform. Clinical malaria episodes after vaccinations were recorded as part of the trial safety monitoring. Binding antibody responses against the Ebola virus (EBOV) glycoprotein (GP) were measured 57 days post dose 1 and 21 days post dose 2 by ELISA and summarized as Geometric Mean Concentrations (GMCs). Geometric Mean Ratios (GMRs) were used to compare groups with different levels of exposure to malaria. Overall, 587 participants, comprising 188 (32%) adults (aged ≥ 18 years) and 399 (68%) children (aged 1-3, 4-11, and 12-17 years), were included in the analysis. There was no evidence that the anti-EBOV-GP antibody GMCs post dose 1 and post dose 2 differed between categories of previous malaria exposure. There was weak evidence that the GMC at 57 days post dose 1 was lower in participants who had had at least one episode of clinical malaria post dose 1 compared to participants with no diagnosed clinical malaria in the same period (GMR = 0.82, 95% CI: 0.69-0.98, p-value = 0.02). However, GMC post dose 2 was not reduced in participants who experienced clinical malaria post-dose 1 and/or post-dose 2 vaccinations. In conclusion, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in individuals with previous exposure to malaria and in those who experience clinical malaria after vaccination. This vaccine regimen is suitable for prophylaxis against Ebola virus disease in malaria-endemic regions.

Do adolescents need a rubella vaccination campaign? Rubella serosurvey among healthy children in Hangzhou, China

ABSTRACT The aim of this study was to evaluate the seroprevalence of rubella antibodies and factors associated with antibody seropositivity after vaccination among healthy children aged 14 and below. A multi-stage stratified random sampling method was employed to recruit participants for the rubella serological test. An enzyme-linked immunosorbent assay method was used to detect human IgG antibodies with avidity for rubella virus in the sera of participants. Univariate and multivariate analyses were used to analyze associations between variables. A total of 778 subjects were included in the subsequent analysis. The overall positive rate of rubella antibody was 83.0% (95%CI: 80.2–85.5%), and the overall geometric mean concentration (GMC) was 58.05 IU/ml. In multivariate analysis, gender, residence, birth year group, and time since the last rubella-containing vaccines (RCV) vaccination were significantly associated with the seroprevalence of rubella antibodies. Our study showed a decreasing trend in rubella antibody positivity and GMC in the population aged five to 14 years. Therefore, we recommend a catch-up dose of RCV for adolescents and young people aged over 14 years not yet vaccinated.

The immunogenicity of the ChAdOx1 nCoV-19 vaccination in participants with underlying comorbidity diseases: A prospective cohort study

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases mortality rates in older adults and those with comorbidities. Individuals with certain comorbidities may have a poor immune response and require early booster vaccines. We aimed to assess the immune response after two doses of ChAdOx1 nCoV-19 vaccine, at 84-day intervals, in participants with the following comorbidities; diabetes mellitus; obesity; cardiovascular disease; chronic kidney disease; rheumatological disease; cirrhosis; hematological disease; hematological malignancy; or solid malignancy. The study was conducted at Chulabhorn Hospital in Thailand, with healthy healthcare workers serving as the control group. Of the 769 participants, 352 were in the healthy cohort and 417 were in the comorbidity cohort, all received at least one dose of vaccine. Anti-RBD total antibody levels were evaluated on Day 0, Day 84, and Day 112. The results at Day 112 (4 weeks after the second dose) showed that individuals with comorbidities had a poor immune response compared to healthy individuals, especially those with hematological malignancy and solid malignancy. The geometric mean concentration (GMC) of anti-RBD antibody in the comorbidity cohort was significantly lower than that in the healthy cohort: 433.66 BAU/ml (95% CI 334.62–562.01) versus 1096.14 BAU/ml (95% CI 1010.26–1189.33), respectively. The geometric mean ratio (GMR) between the two cohorts was 0.40 (95% CI 0.30–0.52, p < .001). This study concluded that individuals with comorbidities, particularly hematological and solid malignancies, had poor immune responses and may require an early booster vaccine to prevent infection and death.