IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-19 DOI: 10.1016/j.vaccine.2024.126461

Mebrihit Arefaine , Asgeir Johannessen , Tilahun Teklehaymanot , Adane Mihret , Dawit Hailu Alemayehu , Mahlet Osman , Andargachew Mulu , Nega Berhe

Background

Historically, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) was considered uncommon in Africa, leading to a reluctant attitude to birth-dose HBV vaccination on the continent. As a randomized trial would be unethical, real-life data are needed to assess the effect of HBV birth-dose vaccine in Africa.

Methods

A multicenter, prospective, observational study of hepatitis B surface antigen (HBsAg)-positive pregnant women and their infants was carried out in Ethiopia, from January 2019 to May 2021. Pregnant women were screened for HBsAg and HIV as part of routine antenatal care and/or delivery, and HBsAg-positive HIV-negative pregnant women were included in the study. HBV birth-dose vaccine and hepatitis B immunoglobulin (HBIg) were recommended but not all newborns received it as it was not national policy. All infants, however, received the pentavalent HBV vaccine at 6, 10, and 14 weeks of age. Vaccination status was confirmed from delivery ward charts and infant vaccination certificates. Infants were tested for HBsAg at 9 months of age and a positive result was taken as evidence of MTCT.

Findings

Of 290 HBsAg-positive pregnant women, 168 mother/infant pairs returned for their 9-month follow-up visit and were included in this analysis. Two of 112 (1.8 %) infants who received birth-dose vaccine with HBIg, and 2 of 23 (8.7 %) who received birth-dose vaccine alone were HBsAg positive at nine months of age, compared to 8 of 33 (24.2 %) who received neither vaccine nor HBIg at birth (p = 0.002). High maternal viral load (>200,000 IU/ml; adjusted odds ratio [AOR] 10.4; 95 % confidence interval [CI] 1.2–92.1) and not receiving HBV birth-dose vaccine nor HBIg (AOR 29.2; 95 % CI 4.0–211.3) were independent predictors of MTCT.

Interpretation

Birth-dose HBV vaccine with or without HBIg significantly reduced the risk of MTCT of HBV in Ethiopia. Improved coverage of birth-dose HBV vaccine should be an urgent priority.

背景：从历史上看，乙型肝炎病毒（HBV）的母婴传播（MTCT）在非洲并不常见，这导致非洲大陆对出生剂量接种 HBV 疫苗持勉强态度。由于随机试验不符合伦理道德，因此需要真实的数据来评估 HBV 出生剂量疫苗在非洲的效果：方法：2019 年 1 月至 2021 年 5 月，在埃塞俄比亚开展了一项针对乙型肝炎表面抗原（HBsAg）阳性孕妇及其婴儿的多中心、前瞻性观察研究。作为常规产前护理和/或分娩的一部分，对孕妇进行了 HBsAg 和 HIV 筛查，HBsAg 阳性、HIV 阴性的孕妇被纳入研究。建议接种 HBV 出生剂量疫苗和乙型肝炎免疫球蛋白 (HBIg)，但并非所有新生儿都接种，因为这不是国家政策。不过，所有婴儿都在 6、10 和 14 周大时接种了五价 HBV 疫苗。疫苗接种情况根据产房记录和婴儿疫苗接种证书进行确认。婴儿在 9 个月大时接受 HBsAg 检测，检测结果呈阳性即为母婴传播的证据：在 290 名 HBsAg 阳性的孕妇中，有 168 对母婴在 9 个月的随访中返回并被纳入本次分析。在 112 名接种了含 HBIg 出生剂量疫苗的婴儿中，有 2 人（1.8%）在 9 个月大时 HBsAg 阳性；在 23 名仅接种了出生剂量疫苗的婴儿中，有 2 人（8.7%）在 9 个月大时 HBsAg 阳性；而在 33 名既未接种疫苗也未接种 HBIg 的婴儿中，有 8 人（24.2%）在出生时 HBsAg 阳性（P = 0.002）。高母体病毒载量（>200,000 IU/ml；调整赔率比 [AOR] 10.4；95 % 置信区间 [CI]1.2-92.1）和未接种 HBV 出生剂量疫苗或 HBIg（AOR 29.2；95 % CI 4.0-211.3）是母婴传播的独立预测因素：在埃塞俄比亚，接种或不接种HBIg的出生剂量HBV疫苗可显著降低HBV母婴传播的风险。当务之急是提高出生剂量 HBV 疫苗的覆盖率。

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引用次数: 0

Evaluation of a multiplexed immunoassay for assessing long-term humoral immunity Orthopoxviruses 评估长期体液免疫正畸病毒的多重免疫测定。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-18 DOI: 10.1016/j.vaccine.2024.126453

Bethany Hicks , Scott Jones , Helen Callaby , Daniel Bailey , Claire Gordon , Tommy Rampling , Catherine Houlihan , Ezra Linley , Simon Tonge , Clarissa Oeser , Rachael Jones , Marcus Pond , Ravi Mehta , Deborah Wright , Bassam Hallis , Cathy Rowe , Ashley Otter

Background

The 2022 Monkeypox virus (MPXV) global outbreak boosted development of multiple serological assays to aid understanding of Mpox immunology.

Objectives

The study aimed to assess a multiplexed solid-phase electrochemiluminescence immunoassay (Meso Scale Discovery (MSD)) for simultaneous detection of antibodies against MPXV, including A35, E8 and M1 antigens, along with corresponding Vaccina Virus (VACV) homologues and demonstrate its accuracy in assessing antibody titres post-vaccination and infection.

Methods

Assay performance was assessed for simultaneous detection of antibodies against MPXV and corresponding VACV antigens. Sensitivity and specificity were evaluated with paediatric negatives (n = 215), pre- and post-IMVANEX vaccinated (n = 80), and MPXV (Clade IIb, n = 39) infected serum samples.

Results

The assay demonstrated high specificity (75.68 % (CI: 69.01–81.29) - 95.98 % (CI:92.54–97.87)) and sensitivity (62.11 % (CI:52.06–71.21) - 98.59 % (CI:92.44 %–99.93 %)) depending on the Orthopoxvirus antigen. Preferential binding was observed between MPXV-infected individuals and MPXV antigens, while vaccinated individuals exhibited increased binding to VACV antigens. These results highlight differential binding patterns between antigen homologues in related viruses.

Conclusion

Overall, this assay demonstrates high sensitivities in detecting antibodies for multiple relevant MPXV and VACV antigens post-infection and post-vaccination, indicating its utility in understanding immune responses to Orthopoxviruses in current and future outbreaks and evaluating the immunogenicity of new-generation Mpox-specific vaccinations.

背景：2022年猴痘病毒（MPXV）在全球爆发，促进了多种血清学检测方法的开发，以帮助人们了解猴痘免疫学：该研究旨在评估一种多重固相电化学发光免疫测定（Meso Scale Discovery (MSD)），用于同时检测MPXV抗体，包括A35、E8和M1抗原，以及相应的疫苗病毒（VACV）同源物，并证明其在评估疫苗接种后和感染后抗体滴度方面的准确性：评估同时检测 MPXV 和相应 VACV 抗原抗体的检测性能。用儿科阴性样本（n = 215）、接种 IMVANEX 疫苗前后的样本（n = 80）和感染 MPXV（Clade IIb，n = 39）的血清样本评估灵敏度和特异性：该检测方法的特异性（75.68 % (CI: 69.01-81.29) - 95.98 % (CI:92.54-97.87 %)）和灵敏度（62.11 % (CI:52.06-71.21) - 98.59 % (CI:92.44 %-99.93 %)）都很高，具体取决于正射血病毒抗原。在 MPXV 感染者与 MPXV 抗原之间观察到了优先结合，而疫苗接种者与 VACV 抗原的结合则有所增加。这些结果凸显了相关病毒抗原同源物之间的不同结合模式：总之，该检测方法在感染后和接种疫苗后检测多种相关的 MPXV 和 VACV 抗原抗体方面表现出很高的灵敏度，表明它在了解当前和未来疫情爆发时对正痘病毒的免疫反应以及评估新一代 Mpox 特异性疫苗的免疫原性方面具有实用价值。

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引用次数: 0

High prevalence of human papillomavirus (HPV) in unvaccinated adolescent girls in South Africa, particularly those living with HIV 南非未接种疫苗的少女，尤其是感染艾滋病毒的少女中人类乳头瘤病毒 (HPV) 感染率很高

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-18 DOI: 10.1016/j.vaccine.2024.126442

Danielle I. Travill , Dorothy A. Machalek , Helen Rees , Zizipho Mbulawa , Admire Chikandiwa , Richard Munthali , Kathy Petoumenos , John M. Kaldor , Sinead Delany-Moretlwe

Introduction

In 2014, South Africa implemented a national two-dose HPV vaccination programme using the bivalent vaccine for girls aged 9 years and older attending Grade 4 at public schools. We assessed HPV prevalence and risk factors among South African adolescent girls and young women (AGYW) aged 17–18 years who were ineligible for vaccination.

Methods

From June to December 2019, we surveyed AGYW aged 17–18 years attending primary care clinics in four South African provinces. Consenting participants completed a questionnaire, underwent HIV counselling and testing, and self-collected a vaginal swab for HPV testing. Samples were tested by Seegene AnyPlex™ II HPV28. We used summary statistics to describe the population characteristics and logistic regression to examine the association between risk factors and high-risk HPV detection.

Results

910 participants were screened, 900 enrolled, 896 had valid HPV results, and 819 were unvaccinated and included in this study. Of these, 248 (30.3 %) were living with HIV and 597 (72.9 %) reported ever having vaginal sex. Overall, 463 (56.5 %) had at least one high-risk HPV detected, and 177 (21.6 %) had HPV16/18 detected. AGYW living with HIV had a higher prevalence of any high-risk HPV (65.3 % vs 52.7 %, p < 0.001) and HPV 16/18 (29.4 % vs 18.2 %, p < 0.001) compared to those without HIV. Multiple infections were also more common in participants living with HIV, with three or more high-risk HPV types detected in 32.3 % compared with 15.4 % of those without HIV (p < 0.001). In multivariate analyses, HIV status (p < 0.001) and higher number of lifetime sexual partners (p-trend<0.001) were associated with high-risk HPV detection.

Conclusions

High-risk HPV was very common in unvaccinated South Africa AGYW, especially among those living with HIV, highlighting the importance of HPV vaccination in settings with high HIV prevalence.

导言2014 年，南非实施了一项全国性的两剂 HPV 疫苗接种计划，为公立学校四年级 9 岁及以上的女生接种二价疫苗。我们评估了不符合接种条件的 17-18 岁南非少女和年轻女性（AGYW）的 HPV 感染率和风险因素。方法从 2019 年 6 月到 12 月，我们对在南非四个省的初级保健诊所就诊的 17-18 岁 AGYW 进行了调查。征得同意的参与者填写了调查问卷，接受了 HIV 咨询和检测，并自行采集了阴道拭子进行 HPV 检测。样本由 Seegene AnyPlex™ II HPV28 进行检测。我们使用摘要统计来描述人群特征，并使用逻辑回归来研究风险因素与高危 HPV 检测之间的关联。结果910 名参与者接受了筛查，900 人注册，896 人获得了有效的 HPV 检测结果，819 人未接种疫苗并纳入本研究。其中，248 人（30.3%）为 HIV 感染者，597 人（72.9%）称曾有过阴道性交。总体而言，463 人（56.5%）至少检测到一种高危 HPV，177 人（21.6%）检测到 HPV16/18。与未感染艾滋病病毒的人相比，感染艾滋病病毒的 AGYW 的高危 HPV 感染率更高（65.3 % vs 52.7 %，p < 0.001），HPV16/18 感染率更高（29.4 % vs 18.2 %，p < 0.001）。多重感染在艾滋病毒感染者中也更为常见，32.3%的感染者检测到三种或三种以上的高危 HPV 类型，而未感染艾滋病毒的感染者只有 15.4%（p <0.001）。在多变量分析中，HIV 感染状况（p <0.001）和终生性伴侣数量较多（p-trend<0.001）与高危 HPV 检测相关。

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引用次数: 0

The risk of postherpetic neuralgia in COVID-19 vaccination-associated herpes zoster: A retrospective cohort study using TriNetX COVID-19 疫苗接种相关带状疱疹的带状疱疹后神经痛风险：使用 TriNetX 进行的回顾性队列研究。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-18 DOI: 10.1016/j.vaccine.2024.126451

Sheng-Hsiang Ma , Tai-Li Chen , Wei-Fan Ou , Wen-Cheng Chao , Hsin-Hua Chen , Chen-Yi Wu

Background

The administration of the COVID-19 vaccine has been linked to the development of herpes zoster (HZ). However, studies examining the clinical outcomes in COVID-19 vaccination-associated and non-COVID-19 vaccination-associated HZ are lacking.

Objective

To investigate the risk of postherpetic neuralgia (PHN) in COVID-19 vaccination associated HZ.

Methods

A total of 7200 patients with COVID-19 vaccination-associated HZ and 7200 matched controls were enrolled from the US Collaborative Network in the TriNetX database. The main outcome of this study was the development of PHN.

Patients were followed-up from 3 months after HZ until PHN diagnoses, withdrawal from the database, or October 8, 2024.

Results

We observed that patients with COVID-19 vaccination-associated HZ had a significantly higher risk of developing PHN as compared to the control group, with hazard ratio of 1.69 (> 3 months), 1.80 (> 6 months), 1.86 (> 1 year), and 1.93 (>2 years), respectively. Additionally, the association remained significant in the stratified analysis, which included sex, age, malignancy status, and initial use of antiviral agents.

Conclusion

This study showed that COVID-19 vaccination-associated HZ demonstrated a significantly higher risk of developing PHN.

背景：接种 COVID-19 疫苗与带状疱疹 (HZ) 的发生有关。然而，目前还缺乏对 COVID-19 疫苗接种相关和非 COVID-19 疫苗接种相关带状疱疹临床结果的研究：目的：调查 COVID-19 疫苗接种相关 HZ 中发生带状疱疹后神经痛（PHN）的风险：方法：从 TriNetX 数据库的美国协作网络中招募了 7200 名 COVID-19 疫苗接种相关 HZ 患者和 7200 名匹配对照。研究的主要结果是出现 PHN。从HZ发生后3个月开始对患者进行随访，直至PHN确诊、退出数据库或2024年10月8日：我们发现，与对照组相比，接种 COVID-19 疫苗相关 HZ 的患者发生 PHN 的风险明显更高，危险比分别为 1.69（>3 个月）、1.80（>6 个月）、1.86（>1 年）和 1.93（>2 年）。此外，在包括性别、年龄、恶性肿瘤状态和最初使用抗病毒药物的分层分析中，这种关联仍然显著：本研究表明，接种 COVID-19 疫苗相关的 HZ 患者罹患 PHN 的风险明显更高。

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引用次数: 0

Longitudinal safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in children aged 4–11 years with juvenile-onset autoimmune inflammatory rheumatic diseases: A prospective multicenter study BNT162b2 mRNA COVID-19 疫苗对 4-11 岁幼年自身免疫性炎症性风湿病患儿的纵向安全性和有效性：一项前瞻性多中心研究

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-17 DOI: 10.1016/j.vaccine.2024.126426

Tali Eviatar , Amit Ziv , Amir Oved , Adi Miller-Barmak , Adi Pappo , Ruth Livny , Gil Amarilyo , Yonatan Butbul Aviel , Rinat Naor , Sara Pel , Victoria Furer , Ori Elkayam , Yosef Uziel , Merav Heshin-Bekenstein

This prospective, longitudinal, multicenter study assessed the safety and efficacy of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine among children 4–11 years-old with autoimmune inflammatory rheumatologic disease (AIIRD), compared to healthy controls. The study was conducted from 11/2021–12/2022 at 4 tertiary pediatric rheumatology units in Israel. Participants received at least 2 vaccine doses. Safety analysis included adverse events and disease activity measures. Efficacy was assessed by COVID-19 infection rates. Immunogenicity was evaluated in a subset of participants using anti- receptor binding domain antibody titers. Thirty-one children with AIIRD and 45 immunocompetent controls with similar baseline characteristics were included. Safety profile was favorable, with mild or no adverse events reported. The adverse event rates were similar in the AIIRD and control groups after the first (27 (60 %) vs. 14 (45.2 %), p = 0.2977) and the second vaccine doses (22 (49.0 %) vs. 18 (58.1 %), p = 0.5799), respectively. AIIRD activity remained stable and low after vaccination. Breakthrough COVID-19 infection rates were similar between groups, with 15 (48.4 %) in the AIIRD vs. 25 (55.6 %) in the control group (p = 0.7029). All reported COVID-19 infections in the AIIRD group and 18 (72 %) in the control group were symptomatic (p = 0.033), although symptoms were generally mild, with no severe disease. The safety of the BNT162b2 COVID-19 vaccine was excellent in children ages 4–11 years with AIIRD and healthy controls. Efficacy between groups was similar.

这项前瞻性纵向多中心研究评估了辉瑞生物技术公司生产的 BNT162b2 mRNA COVID-19 疫苗在 4-11 岁自身免疫性炎症性风湿病 (AIIRD) 儿童中与健康对照组相比的安全性和有效性。该研究于 2021 年 11 月至 2022 年 12 月在以色列的 4 家三级儿科风湿病单位进行。参与者至少接种了两剂疫苗。安全性分析包括不良事件和疾病活动指标。疗效通过 COVID-19 感染率进行评估。使用抗受体结合域抗体滴度对部分参与者的免疫原性进行评估。31名AIIRD患儿和45名免疫功能正常的对照组患儿的基线特征相似。安全性状况良好，不良反应轻微或无。接种第一剂（27（60%）对 14（45.2%），p = 0.2977）和第二剂（22（49.0%）对 18（58.1%），p = 0.5799）后，AIIRD 组和对照组的不良反应发生率相似。接种疫苗后，AIIRD活性保持稳定且较低。各组的 COVID-19 突破性感染率相似，AIIRD 组为 15 例（48.4%），对照组为 25 例（55.6%）（p = 0.7029）。AIIRD 组和对照组分别有 18 例（72%）报告的 COVID-19 感染均有症状（p = 0.033），但症状一般较轻，没有严重疾病。BNT162b2 COVID-19疫苗在4-11岁的AIIRD儿童和健康对照组中安全性极佳。各组之间的疗效相似。

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引用次数: 0

Enhancing HPV vaccine uptake in girls and boys – A qualitative analysis of Canadian school-based vaccination programs 提高女童和男童的 HPV 疫苗接种率--对加拿大校本疫苗接种计划的定性分析

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-17 DOI: 10.1016/j.vaccine.2024.126425

Eve Dubé , Dominique Gagnon , Catherine Pelletier , Jeannette L. Comeau , Audrey Steenbeek , Noni MacDonald , Melissa Kervin , Shannon E. MacDonald , Hana Mitchell , Julie A. Bettinger

The purpose of this study was to better understand barriers and enabling conditions for HPV vaccination in school-based vaccination programs in Canada. Semi-structured interviews were conducted by telephone or in person with parents, nurses, and school staff (n = 50) in three Canadian provinces. Interviews explored views on HPV and HPV vaccination, strengths and weaknesses of the school-based HPV vaccination programs and proposed interventions to increase uptake. Interview transcripts were coded and analyzed thematically using the socio-ecological model. Participants had positive views towards HPV vaccination and school-based offer. They identified barriers and enabling conditions at the individual and interpersonal level (e.g., knowledge, attitudes, behaviours of – and relationships between – parents, nurses, and school personnel), at the organizational level (e.g., allocated resources, information provision, process to ensure informed consent, vaccination setting and environment) and at the community and policy level (e.g., social group values and norms, media coverage around the HPV vaccine). Participants also suggested strategies to reduce identified barriers (e.g., communication interventions, simpler inform consent process). Different layers of barriers and enabling conditions of HPV vaccination in school settings were identified. Tailored interventions remain key to enhance vaccine acceptance and uptake.

本研究旨在更好地了解加拿大校本疫苗接种计划中 HPV 疫苗接种的障碍和有利条件。研究人员通过电话或面对面的方式对加拿大三个省份的家长、护士和学校工作人员（n = 50）进行了半结构化访谈。访谈内容包括对人类乳头瘤病毒和人类乳头瘤病毒疫苗接种的看法、校本人类乳头瘤病毒疫苗接种计划的优缺点以及提高接种率的干预建议。采用社会生态模型对访谈记录进行了编码和专题分析。参与者对 HPV 疫苗接种和校本接种持积极态度。他们指出了个人和人际层面（如家长、护士和学校工作人员的知识、态度和行为以及他们之间的关系）、组织层面（如分配的资源、信息提供、确保知情同意的程序、接种环境）以及社区和政策层面（如社会群体的价值观和规范、媒体对 HPV 疫苗的报道）的障碍和有利条件。与会者还提出了减少已发现障碍的策略（如沟通干预、简化知情同意程序）。在学校环境中接种人类乳头瘤病毒疫苗的障碍和有利条件的层次各不相同。有针对性的干预措施仍是提高疫苗接受度和接种率的关键。

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引用次数: 0

Modelling the epidemiological impact of maternal respiratory syncytial virus (RSV) vaccination in Australia 模拟澳大利亚产妇呼吸道合胞病毒 (RSV) 疫苗接种的流行病学影响

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-17 DOI: 10.1016/j.vaccine.2024.126418

Allen L. Nazareno , Anthony T. Newall , David J. Muscatello , Alexandra B. Hogan , James G. Wood

Background

Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among infants. A maternal RSV vaccine that protects young infants has recently been approved for registration in Australia. We estimated the population benefits of a future year-round maternal RSV vaccination program in terms of prevented RSV infections and hospitalisations in Australia.

Methods

We described RSV transmission using an age-structured compartmental model calibrated to Australian aggregated monthly RSV-coded hospitalisations in children aged <5 years. We accounted for mother and infant interactions in the model to capture herd effects more realistically. Using the model, we estimated the annual age-specific RSV infections and hospitalisations prevented for a range of assumptions for vaccine efficacy, coverage, and durability to estimate the future impact of year-round maternal RSV vaccination on infants and the wider population.

Results

Assuming base case vaccine efficacy, 6 months duration of protection and 70% coverage, RSV hospitalisations were predicted to fall by 60% (from 3.0 to 1.2 per 100 persons) in infants aged <3 months and 40% (from 1.9 to 1.1 per 100 persons) in 3–5-month-olds. These benefits were primarily due to direct protection to infants of vaccinated mothers. This vaccine program was predicted to reduce the population-level RSV infection by about 4%. Coverage and duration assumptions were influential, with higher coverage leading to larger declines in infants <6 months, and increased duration of protection leading to additional declines in infection and hospitalisation risk in older infants aged 6–8 months.

Conclusions

With vaccine uptake similar to that achieved for other maternal vaccines in Australia, a year-round RSV maternal vaccination program is predicted to approximately halve the number of RSV hospitalisations in infants younger than 6 months. There was a small herd effect predicted in the base case but potential for larger benefits if vaccine coverage or the duration of protection exceeds base case assumptions.

背景呼吸道合胞病毒（RSV）是婴儿呼吸道疾病的主要病因。澳大利亚最近批准注册了一种可保护幼儿的母体 RSV 疫苗。我们估算了澳大利亚未来全年母体 RSV 疫苗接种计划在预防 RSV 感染和住院方面的人口效益。方法我们使用一个年龄结构分区模型来描述 RSV 传播，该模型根据澳大利亚每月汇总的 5 岁儿童 RSV 编码住院病例进行校准。我们在模型中考虑了母亲和婴儿的相互作用，以更真实地反映群体效应。利用该模型，我们估算了在疫苗效力、覆盖率和持久性等一系列假设条件下每年预防的特定年龄 RSV 感染和住院人数，从而估算出全年为母亲接种 RSV 疫苗对婴儿和更广泛人群的未来影响。结果假设基本情况下的疫苗效力、6 个月的保护期和 70% 的覆盖率，预计 3 个月大婴儿的 RSV 住院率将下降 60%（从每 100 人 3.0 例降至 1.2 例），3-5 个月大婴儿的 RSV 住院率将下降 40%（从每 100 人 1.9 例降至 1.1 例）。这些益处主要归功于接种疫苗的母亲对婴儿的直接保护。据预测，该疫苗计划可将人群 RSV 感染率降低约 4%。覆盖率和持续时间假设具有影响力，覆盖率越高，6 个月婴儿的感染率下降幅度越大，保护持续时间越长，6-8 个月大婴儿的感染和住院风险下降幅度越大。结论如果疫苗接种率与澳大利亚其他母体疫苗的接种率相似，全年 RSV 母体疫苗接种计划预计可将 6 个月以下婴儿的 RSV 住院人数减少约一半。基础案例预测的群体效应较小，但如果疫苗覆盖率或保护持续时间超过基础案例假设，则有可能产生更大的效益。

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引用次数: 0

Oral paratuberculosis vaccine efficacy and mucosal immunity in cattle 牛口服副结核病疫苗的效力和黏膜免疫力

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-17 DOI: 10.1016/j.vaccine.2024.126447

Razieh Eshraghisamani , Antonio Facciuolo , Jeroen De Buck

Mycobacterium avium subsp. paratuberculosis (MAP) primarily invades ruminants' small intestine via the Peyer's patches in the ileum and jejunum. Despite ongoing efforts to develop effective MAP vaccines, the effects of live-attenuated vaccines on mucosal immunity remain poorly understood. Previous studies indicate that the BacA oral vaccine confers localized protection against MAP in the ileum and ileocecal valve of calves, but not in the jejunum. This protection correlates with heightened levels of peripheral blood immune cells exhibiting pro-inflammatory and memory traits. This study aimed to evaluate immune responses induced by oral BacA vaccination in the ileum and jejunum Peyer's patches, comparing protection at both sites through mucosal immune cell profiling and RNA-seq transcriptome analyses. It represents the first exploration of mucosal immune responses in Peyer's patches following oral MAP vaccination.

Oral BacA immunization increased CD4 + IFNγ+ and CD4 + TNFα+ cell frequencies, along with the T effector memory to T central memory cell ratio, in the ileum and jejunum of BacA-vaccinated animals challenged with wildtype MAP, compared to the infection control group challenged solely with wildtype MAP. Immune cells isolated from the ileum of vaccinated-challenged animals exhibited significant upregulation in IFNγ, IP-10, TNFα, IL-2, IL-15, and IL-17 expression upon restimulation compared to the uninfected control group, whereas minimal differences were observed in the jejunum under similar conditions. RNA-seq data further indicated a more robust host response in the ileum across all experimental groups. Gene ontology analyses revealed genes associated with increased phagocytic and apoptotic activities in the vaccinated-challenged group.

Overall, the BacA oral vaccine's effectiveness appears to vary primarily due to differences in antigen-specific gene expression between the ileum and jejunum, with the ileum showing a more robust host response. Understanding these effects on young calves' mucosal immunity and how live vaccines modulate immune responses is crucial for advancing mucosal vaccine development against MAP.

副结核分枝杆菌（MAP）主要通过回肠和空肠的派尔氏斑侵入反刍动物的小肠。尽管人们一直在努力开发有效的 MAP 疫苗，但对减毒活疫苗对粘膜免疫的影响仍然知之甚少。先前的研究表明，BacA 口服疫苗可在小牛回肠和回盲瓣局部产生抗 MAP 的保护作用，但在空肠却没有。这种保护作用与外周血免疫细胞水平升高有关，外周血免疫细胞表现出促炎症和记忆特征。本研究旨在评估口服 BacA 疫苗在回肠和空肠派尔氏斑诱导的免疫反应，通过粘膜免疫细胞图谱分析和 RNA-seq 转录组分析比较这两个部位的保护作用。与仅接种野生型MAP的感染对照组相比，接种BacA疫苗的动物回肠和空肠中的CD4 + IFNγ+和CD4 + TNFα+细胞频率以及T效应记忆细胞与T中枢记忆细胞的比率均有所增加。与未感染的对照组相比，从接种疫苗的动物回肠中分离出的免疫细胞在再刺激时表现出 IFNγ、IP-10、TNFα、IL-2、IL-15 和 IL-17 表达的显著上调，而在类似条件下空肠中观察到的差异很小。RNA-seq数据进一步表明，在所有实验组中，回肠的宿主反应更强。基因本体分析表明，接种疫苗组的吞噬细胞和细胞凋亡活动增加了相关基因。总之，BacA 口服疫苗的效果似乎主要因回肠和空肠中抗原特异性基因表达的差异而异，回肠显示出更强的宿主反应。了解这些对幼犊粘膜免疫的影响以及活疫苗是如何调节免疫反应的，对于推进针对MAP的粘膜疫苗开发至关重要。

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引用次数: 0

Bacillus Calmette-Guérin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau 接种卡介苗可诱导 50 岁以上成年人形成训练有素的先天免疫表型：几内亚比绍的随机试验

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-17 DOI: 10.1016/j.vaccine.2024.126439

Mike Leonardus Theodorus Berendsen , Pauli Bles , Louise Charlotte Johanna de Bree , Kristoffer Jarlov Jensen , Clara Clipet Jensen , Christian Wejse , Delfim Vicente Mendes , Mihai Gheorghe Netea , Christine Stabell Benn

Background

The beneficial effects of Bacillus Calmette-Guérin (BCG) as an intervention against non-mycobacterial infections have been extensively studied in randomized trials. These non-specific effects have been linked to a heterologous increase of pro-inflammatory cytokine production by innate immune cells. It is unknown if BCG induces such responses in older individuals from TB-endemic countries.

Methods

In a single-blinded trial in Guinea-Bissau, 40 adults over 50 years of age were randomized 1:1 in a block of 40 to intradermal injection of BCG-Japan (intervention) or solvent (placebo). Production of interleukin (IL)-1β, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was measured by ELISA in supernatant of peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis and heterologous pathogens. The trial was registered at clinicaltrials.gov (NCT02953327).

Findings

Between January 25 and March 7, 2017, 40 individuals were randomized. Two months after vaccination, BCG-Japan recipients (n = 11) had higher production of IFN-γ to M. tuberculosis stimulation (Geometric mean ratio (GMR): 3·91 [95 % Confidence Interval (CI), 1·53–9·96]) and increased release of the pro-inflammatory innate cytokines IL-1β, IL-6 and TNF-α to non-specific stimuli (GMR TNF-α: 1·47 [95 % CI, 0·98–2·19]) than their controls (n = 13). Both the specific and non-specific responses were more pronounced among those with a positive QuantiFERON at baseline.

Interpretation

BCG-Japan can induce a trained immunity phenotype in older adults. These effects were particularly strong in previously M. tuberculosis exposed individuals. Future randomized trials are needed to determine BCG's potential to protect the older populations from infections-driven morbidity and mortality.

背景在随机试验中对卡介苗（Bacillus Calmette-Guérin，BCG）作为非霉菌感染干预措施的有益效果进行了广泛研究。这些非特异性效果与先天性免疫细胞产生的促炎细胞因子的异源性增加有关。在几内亚比绍进行的一项单盲试验中，40 名 50 岁以上的成年人按 1:1 的比例被随机分组，皮内注射日本卡介苗（干预）或溶剂（安慰剂）。通过酶联免疫吸附试验测定了结核分枝杆菌和异源病原体刺激的外周血单核细胞上清液中白细胞介素（IL）-1β、IL-6、IL-10、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的分泌情况。该试验已在 clinicaltrials.gov （NCT02953327）上注册。研究结果2017年1月25日至3月7日期间，40人被随机分配。接种卡介苗两个月后，日本卡介苗接种者（n = 11）对结核杆菌刺激产生的 IFN-γ 更高（几何值）。与对照组（n = 13）相比，日本卡介苗接种者（n = 11）在结核杆菌刺激下产生的 IFN-γ 更高（几何平均比（GMR）：3-91 [95 % 置信区间（CI），1-53-9-96]），在非特异性刺激下释放的促炎性先天性细胞因子 IL-1β、IL-6 和 TNF-α 更高（GMR TNF-α：1-47 [95 % CI，0-98-2-19]）。在基线定量因子呈阳性的人群中，特异性和非特异性反应都更为明显。这些效果在以前接触过结核杆菌的人群中尤为明显。未来需要进行随机试验，以确定卡介苗在保护老年人免受感染导致的发病率和死亡率方面的潜力。

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引用次数: 0

Intranasal booster with SARS-CoV-2 RBD protein fused to E. coli enterotoxin a subunit after primary mRNA vaccination in mice 在对小鼠进行初级 mRNA 疫苗接种后，用融合了大肠杆菌肠毒素 a 亚基的 SARS-CoV-2 RBD 蛋白进行鼻内加强免疫

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine

Pub Date : 2024-10-16 DOI: 10.1016/j.vaccine.2024.126448

He-Chin Hsieh , Chung-Chu Chen , Wen-Chun Liu , Suh-Chin Wu

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 led to the coronavirus infection diseases 2019 (COVID-19) pandemic, significantly impacting global public health and the economy. Numerous COVID-19 vaccines based on the receptor binding domain (RBD) of SARS-CoV-2 spike protein have been developed, utilizing various protein expression platforms and adjuvant systems. In a previous study, we reported using the direct fusion of the A subunit of type IIb E. coli heat-labile enterotoxin with the SARS-CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate (Hsieh et al., 2023). In this study, we investigated the effects of an intranasal booster of RBD-LTA/RBD mixture proteins after one or two doses of intramuscular bivalent BA.4/5 mRNA vaccination over 17 and 35 weeks. Our results indicate that the intranasal RBD-LTA/RBD mixture proteins booster maintains high levels of anti-RBD IgG and neutralizing antibodies, comparable to those elicited by a two-dose mRNA vaccination regimen. An additional RBD-LTA/RBD mixture proteins booster significantly increased antibody titers, demonstrating the potential of this approach for long-term immunity against SARS-CoV-2. Our findings suggest that combining primary mRNA vaccination with an intranasal RBD-LTA/RBD mixture proteins booster can effectively sustain antibody levels over extended periods, providing a promising strategy for long-term protection against SARS-CoV-2 and its variants.

2019 年爆发的严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）导致了 2019 年冠状病毒感染病（COVID-19）的大流行，对全球公共卫生和经济造成了重大影响。利用各种蛋白表达平台和佐剂系统，基于SARS-CoV-2尖峰蛋白的受体结合域（RBD）开发了许多COVID-19疫苗。在之前的一项研究中，我们报道了将 IIb 型大肠杆菌热嗜性肠毒素的 A 亚基与 SARS-CoV-2 RBD 蛋白（RBD-LTA）直接融合作为鼻内候选疫苗（Hsieh 等人，2023 年）。在本研究中，我们调查了在 17 周和 35 周内肌肉注射一剂或两剂二价 BA.4/5 mRNA 疫苗后鼻内加强注射 RBD-LTA/RBD 混合蛋白的效果。我们的研究结果表明，鼻内注射 RBD-LTA/RBD 混合蛋白加强剂可维持高水平的抗 RBD IgG 和中和抗体，与两剂 mRNA 疫苗接种方案所产生的抗体水平相当。额外的 RBD-LTA/RBD 混合蛋白强化剂可显著提高抗体滴度，这表明这种方法具有长期免疫 SARS-CoV-2 的潜力。我们的研究结果表明，将初级 mRNA 疫苗接种与鼻内注射 RBD-LTA/RBD 混合蛋白加强剂相结合，可以有效地长期维持抗体水平，为长期抵御 SARS-CoV-2 及其变种提供了一种可行的策略。

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引用次数: 0