Seroprevalence of IgG and IgM antibodies to Haemophilus influenzae type a in Canadian children

BackgroundOver the last 2 decades, Haemophilus influenzae type a (Hia) has emerged as a significant cause of invasive disease in some geographic regions and populations. Recognition of the importance of Hia in the etiology of serious disease, particularly in young children, prompted the development of a new protein-capsular polysaccharide conjugate vaccine, similar in design to a vaccine against H. influenzae type b. At present, understanding of Hia immunology is incomplete; the immunological correlate of protection against invasive disease is unknown.MethodsOur objective was to study Hia antibody in children of various ages residing in a Canadian province with low incidence rates of invasive disease. The enzyme-linked immunosorbent assays were performed to quantify plasma IgG and IgM specific to Hia capsular polysaccharide in 133 children (3 months to 16 years).ResultsBoth anti-Hia IgG and IgM concentrations increased with age and were significantly higher in older children; a positive correlation between age and concentrations of Hia antibody was found. IgM antibody concentrations were significantly higher than IgG, with mean IgM concentrations over 10 times larger than IgG across all age groups.ConclusionsThe steady rise of naturally acquired, Hia-specific IgG and IgM concentrations in a pediatric population with low incidence rates of invasive Hia disease suggests the exposure to some cross-reactive environmental antigens as a major source of the antibody. However, the carriage rates of Hia in the region are unknown and further seroepidemiological studies are warranted. Although natural antibody may protect certain population groups against invasive disease, immunization of younger children will be essential to prevent serious infections if Hia continues to spread across North America.     

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study

BackgroundDuring the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands.MethodsWe estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence.ResultsWith a decrease in numbers of sex partners of 15–25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred.ConclusionsDespite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

BackgroundCurrently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy.ObjectiveTo determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult.MethodsThis is a prospective cohort study of adult aged 18–59 years who received 2-dose SV at 14–35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×10¹⁰ viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route.ResultsFrom August2021, 100 adults with median age of 46 years(IQR 41–52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7–26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4–125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2–96.8) at day14, 73.1% inhibition (66.7–80.2) at day90, and 22.7% inhibition (14.9–34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and ?37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9–2343.2) at day14 and 744.6 BAU/ml(650.1–852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83–1.20) at day14, and 0.82(0.66–1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister.ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.     

2018 ATC/TTS器官移植前沿热点回顾及进展概述

重点概述2018年美国移植大会及第27届国际移植大会有关器官移植基础、临床及转化医学研究的前沿热点及最新进展，包括供者特异性抗体、抗体介导排斥反应、临床免疫耐受、供器官合理利用、供肝保存新技术应用及移植相关病毒感染等概要内容。     

Skewed B cell receptor repertoire and reduced antibody avidity in patients with DOCK8 deficiency

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8⁺ T‐cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary.     

Rabies virus glycoprotein serology ELISA for measurement of neutralizing antibodies in sera of vaccinated human subjects

BackgroundVaccination provides protection against infection by inducing VNAs mainly against RABV surface GP. The measurement of VNAs to RABV is commonly used to assess the level of immunity in humans and animals after vaccination. A VNA titer of ≥ 0.5 IU/mL of sera indicates adequate response to vaccination. Here, we report the development and validation of a RABV GP serology ELISA kit for semi-quantitative measurement of VNA titers in sera of vaccinated human subjects.MethodsUsing a recombinant RABV GP expressed in mammalian cells as the capture antigen, the ELISA method was established using HuMAb NM57 reference initially and HRIG reference subsequently. The limit of detection (LOD), linear range, reproducibility, and precision of the method were examined. Specificity and sensitivity were established to assess the diagnostic accuracy.ResultsRABV GP for ELISA plate coating and optimal dilution of human serum sample was 1 µg/mL and 1:20, respectively. Multiple assays were carried out by different technicians at different laboratories for assay standardization. Using the HRIG reference, the LOD was found to be 0.02–0.06 IU/mL and the linear range was 0.2–10.0 IU/ mL. The inter-assay CVs were in the range of 6.60–10.79%, indicating the reproducibility. None of the 12 known negative human sera, tested positive by ELISA, highlighting the specificity. A total of 415 unknown positive human sera were double-blind tested by the RFFIT and ELISA. The VNA titer cut-off value of ELISA was set at 1.5 IU/mL to ensure no false-positive. The diagnostic specificity and sensitivity were 100% and 91.1%, respectively.ConclusionsThe validation data characterize this ELISA as a suitable method for semi-quantitative measurement of VNA titers in human serum samples to assess vaccination status. The ELISA kit can offer simplicity, speed, low cost and high throughput, making it a practical tool for monitoring the immune response following vaccination.     

MRI findings in pediatric neuromyelitis optica spectrum disorder with MOG antibody: Four cases and review of the literature

Background

Myelin oligodendrocyte glycoprotein antibodies (MOG Abs) are frequently detected in pediatric acquired demyelinating syndrome (ADS), and MOG-Ab-positive ADS differs from multiple sclerosis (MS) and aquaporin-4 (AQP4)-Ab-positive neuromyelitis optica spectrum disorder (NMOSD) in terms of age distribution, therapeutic response, and prognosis.