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Human papillomavirus and occupational exposure: The need for vaccine provision for healthcare providers. 人类乳头瘤病毒与职业暴露:为医护人员提供疫苗的必要性。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-05-21 DOI: 10.1080/21645515.2024.2342622
Selim Afsar, Maksuda Hossain, Muntaha Islam, Hailey Simmonds, Ashley A Stillwell, Kristina A Butler

To probe the understanding of healthcare providers regarding occupational exposure to human papillomavirus and their knowledge about human papillomavirus vaccination in relation to the American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations. In this cross-sectional study, the healthcare providers at Mayo Clinic Arizona, Florida, and Minnesota were delivered an electronic survey. The survey was completed by 349 healthcare providers, with one respondent excluded for inconsistent entry. The mean age of respondents was 42.7 ± 10.9, and of those, 68% were female and 32% were male. Of the unvaccinated respondents, 43.3% were ≤ 45 y of age (eligible for vaccination), while those vaccinated formed 41% of the respondents. Healthcare providers are highly concerned about their cancer safety, as shown by their awareness of occupational human papillomavirus hazards and broad knowledge about vaccine efficacy. The use of personal protective equipment varied widely, including eyewear, double gloving, procedural face mask, N95 face mask, and/or nothing. Human papillomavirus and cancer risk was clearly perceived by healthcare providers. For professions, pairwise comparisons revealed that nurse practitioners, physician assistants, certified registered nurse anesthetists, and allied healthcare providers had lower scores than medical doctors. Despite the high level of understanding among healthcare providers of occupational human papillomavirus exposure, only a few of them knew of the recommendations of the ASCPP for vaccination of healthcare providers treating human papillomavirus-related diseases. In such cases, most of those surveyed embraced vaccination, which was considered 100% safe by medical doctors and allied health professionals.

目的:调查医疗服务提供者对人类乳头瘤病毒职业暴露的了解,以及他们根据美国阴道镜和宫颈病理学协会 (ASCCP) 的建议接种人类乳头瘤病毒疫苗的知识。在这项横断面研究中,亚利桑那州、佛罗里达州和明尼苏达州梅奥诊所的医疗服务提供者接受了一项电子调查。共有 349 名医疗服务提供者完成了调查,其中一名受访者因输入不一致而被排除在外。受访者的平均年龄为 42.7 ± 10.9 岁,其中 68% 为女性,32% 为男性。在未接种疫苗的受访者中,43.3%的人年龄小于 45 岁(符合接种条件),而接种疫苗的受访者占 41%。医疗服务提供者高度关注自身的癌症安全,这体现在他们对职业性人类乳头瘤病毒危害的认识和对疫苗功效的广泛了解上。个人防护设备的使用情况差异很大,包括眼镜、双层手套、程序性口罩、N95 口罩和/或什么都不使用。医疗服务提供者对人类乳头瘤病毒和癌症风险有明确的认识。就职业而言,成对比较显示,执业护士、医生助理、注册麻醉师和专职医疗保健提供者的得分低于医生。尽管医护人员对职业性人类乳头瘤病毒暴露的了解程度很高,但其中只有少数人知道 ASCPP 对治疗人类乳头瘤病毒相关疾病的医护人员接种疫苗的建议。在这种情况下,大多数受访者接受了疫苗接种,医生和专职医疗人员认为疫苗接种是 100% 安全的。
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引用次数: 0
A latent class analysis of factors influencing preferences for infant respiratory syncytial virus (RSV) preventives among pregnant people in the United States. 对影响美国孕妇对婴儿呼吸道合胞病毒 (RSV) 预防药物偏好的因素进行潜类分析。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-06-07 DOI: 10.1080/21645515.2024.2358566
Martine C Maculaitis, Brett Hauber, Kathleen M Beusterien, Oliver Will, Lewis Kopenhafer, Amy W Law, Jeffrey T Vietri, Joseph C Cappelleri, Joshua R Coulter, Sarah Pugh, Kimberly M Shea

A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.

最近批准了一种母体疫苗和长效单克隆抗体 (mAb),用于保护婴儿免受呼吸道合胞病毒 (RSV) 的感染。我们确定了对 RSV 预防药物有不同偏好的孕妇亚群,以及与亚群成员相关的受访者特征。我们对美国孕妇进行了在线调查,包括离散选择实验(DCE)。RSV 预防药物的属性包括有效性、RSV 流行季节的保护持续时间、注射对象/时间、预防类型(疫苗或 mAb)以及接受注射所需的就诊类型。在 DCE 选择任务中,孕妇在属性水平不同的两种假设预防方案和一种无预防方案中进行选择。数据分析采用了逻辑回归,包括潜类分析(LCA)。在 992 名孕妇(平均年龄:30.0 岁)中,60.3% 的孕妇将迎来第二胎/晚育。LCA 确定了三个偏好亚群:"有效性"(预防选择主要受有效性提高的驱动;51.4% 的类别成员概率)、"季节性"(预防选择主要受 RSV 流行季节保护持续时间延长的驱动;39.2% 的类别成员概率)和 "无预防性"(经常选择无预防性选项;9.4% 的类别成员概率)。有效性 "和 "季节性 "首选母体疫苗而非 mAb;"无预防性 "首选 mAb。认为 RSV 对婴儿很严重、健康知识水平较高和家庭收入较低与 "有效 "相关。认为 RSV 对孕妇很严重与 "季节 "有关。认为 RSV 对孕妇不严重和没有工作与 "无预防性 "有关。孕妇亚群对 RSV 预防措施的偏好各不相同。大多数孕妇更愿意接种母体疫苗,尽管有些人可能更愿意接受其他预防方案。
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引用次数: 0
Epidemic patterns of the different influenza virus types and subtypes/lineages for 10 years in Chongqing, China, 2010-2019. 2010-2019 年中国重庆 10 年间不同流感病毒类型和亚型/系谱的流行模式。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-06-07 DOI: 10.1080/21645515.2024.2363076
Xiaoqing Fu, Jiang Long, Yu Xiong, Zhifeng Li, Jule Yang, Dechao Tian, Zhourong Li, Shuang Yang, Li Qi

To optimize seasonal influenza control and prevention programs in regions with potentially complicated seasonal patterns. Descriptive epidemiology was used to analyze the etiology of influenza, and chi-square tests were used to compare the epidemic patterns among different influenza virus types and subtypes/lineages. From January 2010 to December 2019, a total of 63,626 ILI cases were reported in Chongqing and 14,136 (22.22%) were laboratory-confirmed influenza cases. The proportions of specimens positive for influenza A and influenza B were 13.32% (8,478/63,626) and 8.86% (5,639/63,626), respectively. The proportion of positive specimens for influenza A reached the highest in winter (23.33%), while the proportion of positive specimens for influenza B reached the highest in spring (11.88%). Children aged 5-14 years old had the highest proportion of positive specimens for influenza. The influenza virus types/subtypes positive was significantly different by seasons and age groups (P<.001), but not by gender (p = .436). The vaccine strains were matched to the circulating influenza virus strains in all other years except for 2018 (vaccine strain was B/Colorado/06/2017; circulating strain was B/Yamagata). The study showed significant variations in epidemic patterns, including seasonal epidemic period and age distributions, among different influenza types, subtypes/lineages in Chongqing. Influenza vaccines matched to the circulating influenza virus strain in nine of the ten years. To prevent and mitigate the influenza outbreaks in this area, high risk population, especially children aged 5-14 years, are encouraged to get vaccinated against influenza before the epidemic seasons.

在季节模式可能复杂的地区优化季节性流感防控计划。采用描述性流行病学分析流感病原学,采用卡方检验比较不同流感病毒类型和亚型/系之间的流行规律。2010年1月至2019年12月,重庆共报告63,626例ILI病例,其中14,136例(22.22%)为实验室确诊的流感病例。甲型流感和乙型流感阳性标本比例分别为13.32%(8478份/63626例)和8.86%(5639份/63626例)。冬季的甲型流感阳性样本比例最高(23.33%),而春季的乙型流感阳性样本比例最高(11.88%)。5-14 岁儿童的流感阳性样本比例最高。不同季节和年龄组的流感病毒阳性类型/亚型有显著差异(Pp = .436)。除 2018 年外(疫苗毒株为 B/科罗拉多/06/2017;流行毒株为 B/山形),其他年份的疫苗毒株均与流行的流感病毒毒株相匹配。研究显示,重庆不同流感类型、亚型/系之间的流行模式存在明显差异,包括季节性流行期和年龄分布。在十年中,有九年的流感疫苗与流行的流感病毒株相匹配。为预防和减少流感在该地区的爆发,鼓励高危人群,尤其是 5-14 岁儿童,在流感流行季节前接种流感疫苗。
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引用次数: 0
Immunogenicity of intranasal vaccine based on SARS-CoV-2 spike protein during primary and booster immunizations in mice. 基于 SARS-CoV-2 穗状病毒的鼻内疫苗在小鼠初次免疫和加强免疫期间的免疫原性。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-06-16 DOI: 10.1080/21645515.2024.2364519
Huijie Yang, Ying Xie, Shuyan Li, Chunting Bao, Jiahao Wang, Changgui Li, Jiaojiao Nie, Yaru Quan

Mucosal immunity plays a crucial role in combating and controlling the spread of highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recombinant subunit vaccines have shown safety and efficacy in clinical trials, but further investigation is necessary to evaluate their feasibility as mucosal vaccines. This study developed a SARS-CoV-2 mucosal vaccine using spike (S) proteins from a prototype strain and the omicron variant, along with a cationic chitosan adjuvant, and systematically evaluated its immunogenicity after both primary and booster immunization in mice. Primary immunization through intraperitoneal and intranasal administration of the S protein elicited cross-reactive antibodies against prototype strains, as well as delta and omicron variants, with particularly strong effects observed after mucosal vaccination. In the context of booster immunization following primary immunization with inactivated vaccines, the omicron-based S protein mucosal vaccine resulted in a broader and more robust neutralizing antibody response in both serum and respiratory mucosa compared to the prototype vaccine, enhancing protection against different variants. These findings indicate that mucosal vaccination with the S protein has the potential to trigger a broader and stronger antibody response during primary and booster immunization, making it a promising strategy against respiratory pathogens.

粘膜免疫在抗击和控制高度变异的严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)的传播中起着至关重要的作用。重组亚单位疫苗在临床试验中显示出了安全性和有效性,但要评估其作为粘膜疫苗的可行性还需要进一步的研究。本研究利用原型毒株和奥米克变异株的尖峰(S)蛋白以及阳离子壳聚糖佐剂开发了一种 SARS-CoV-2 粘膜疫苗,并系统评估了小鼠初次免疫和加强免疫后的免疫原性。通过腹腔注射和鼻内注射 S 蛋白进行初次免疫,可产生针对原型菌株以及 delta 和 omicron 变体的交叉反应抗体,粘膜接种后效果尤为显著。在灭活疫苗初次免疫后的加强免疫中,与原型疫苗相比,基于奥米克龙的 S 蛋白粘膜疫苗可在血清和呼吸道粘膜中产生更广泛、更强大的中和抗体反应,从而增强对不同变异株的保护。这些研究结果表明,S 蛋白粘膜疫苗接种有可能在初次免疫和加强免疫期间引发更广泛和更强的抗体反应,使其成为一种很有前途的抗呼吸道病原体策略。
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引用次数: 0
Correction. 更正。
IF 4.4 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-07-01 DOI: 10.1080/15384047.2024.2375109
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引用次数: 0
COVID-19 vaccination perspectives among patients with Long COVID: A qualitative study. 长COVID患者对COVID-19疫苗接种的看法:一项定性研究。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-03-26 DOI: 10.1080/21645515.2024.2327663
Sarah R MacEwan, Saurabh Rahurkar, Willi L Tarver, Alice A Gaughan, Laura J Rush, Andrew Schamess, Ann Scheck McAlearney

Individuals who have Long COVID may have unique perspectives about COVID-19 vaccination due to the significant impact that COVID-19 has had on their lives. However, little is known about the specific vaccination perspectives among this patient population. The goal of our study was to improve our understanding of perspectives about COVID-19 vaccines among individuals with Long COVID. Interviews were conducted with patients receiving care at a post-COVID recovery clinic. Deductive thematic analysis was used to characterize participant perspectives according to the vaccine acceptance continuum framework, which recognizes a spectrum from vaccine acceptance to refusal. From interviews with 21 patients, we identified perspectives across the continuum of vaccine acceptance. These perspectives included acceptance of vaccines to prevent future illness, concerns about vaccine side effects on Long COVID symptoms, and refusal of vaccines due to perceived natural immunity. A limitation of our study is that these perspectives are specific to individuals receiving care at one post-COVID recovery clinic. In conclusion, our study demonstrates that some patients with Long COVID are uncertain about COVID-19 vaccines and boosters but may also be amenable to conversations that impact future vaccination acceptance. Patient perspectives should be considered when communicating recommendations for COVID-19 vaccinations to this population.

由于 COVID-19 对他们的生活产生了重大影响,长效 COVID 患者可能对 COVID-19 疫苗接种有独特的看法。然而,人们对这一患者群体的具体疫苗接种观点知之甚少。我们的研究旨在加深我们对长COVID-19患者接种COVID-19疫苗的看法的了解。我们对在 COVID 后康复诊所接受治疗的患者进行了访谈。我们采用演绎主题分析法,根据疫苗接受连续体框架来描述参与者的观点。通过对 21 名患者的访谈,我们确定了疫苗接受连续体的观点。这些观点包括接受疫苗以预防未来的疾病、担心疫苗对长COVID症状的副作用,以及因认为疫苗具有天然免疫功能而拒绝接受疫苗。我们研究的局限性在于,这些观点仅针对在一家后 COVID 恢复诊所接受治疗的个人。总之,我们的研究表明,一些长COVID患者对COVID-19疫苗和强化剂并不确定,但也可能愿意接受影响未来疫苗接种接受度的谈话。在向这类人群传达 COVID-19 疫苗接种建议时,应考虑患者的观点。
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引用次数: 0
Herpes zoster in older adults: Impact on carbon footprint in the United States. 老年人带状疱疹:对美国碳足迹的影响。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-05-03 DOI: 10.1080/21645515.2024.2335722
Desmond Curran, Jacopo Bitetti, Imogen Catterall, Stephen Wincott

We provide estimates for (I) annual herpes zoster (HZ) cases, (II) carbon costs related to healthcare utilization, and (III) annual carbon emissions due to HZ among ≥50 years of age (YOA) United States (US) population. We estimated the annual number of HZ cases in the US based on available incidence data and demographic data of individuals ≥50 YOA. Both the healthcare resource utilization (HCRU) associated with HZ cases and the unit carbon dioxide equivalent (i.e. CO2e) costs associated with each type of HCRU in the US were estimated based on literature and studies available online. The carbon footprint associated with HZ annually among US adults ≥50 YOA was estimated by multiplying the unit carbon estimates by the HCRU. In the US population aged ≥50 YOA in 2020 (i.e. approximately 118 million), approximately 1.1 million cases of HZ occur annually assuming no vaccination. Based on 2 sources of HCRU the average kgCO2e per HZ patient ranged from 61.0 to 97.6 kgCO2e, with values by age group ranging from 40.9 kgCO2e in patients aged 50-59 to 195.9 kgCO2e in patients ≥80 YOA. The total annual HZ associated carbon ranged between 67,000 and 107,000 tons of CO2e in the US population aged ≥50 YOA. The impact of HZ on carbon footprint in the US results in considerable greenhouse gas (GHG)emissions. Assuming no vaccination, the burden of HZ is projected to rise over the coming years with the aging populations consequently worsening its impact on GHG emissions. (Figure 1).

我们提供了美国≥50 岁(YOA)人口中(I)带状疱疹(HZ)年病例数、(II)与医疗保健使用相关的碳成本以及(III)HZ 年碳排放量的估计值。我们根据现有的发病率数据和年龄≥50 岁人群的人口统计数据估算了美国每年的 HZ 病例数。与 HZ 病例相关的医疗资源利用率 (HCRU) 以及与美国各类 HCRU 相关的单位二氧化碳当量(即 CO2e)成本都是根据网上的文献和研究进行估算的。通过将单位碳估算值乘以 HCRU,估算出美国年龄≥50 岁的成年人每年与 HZ 相关的碳足迹。在 2020 年年龄≥50 岁的美国人口(即约 1.18 亿人)中,假设不接种疫苗,每年约有 110 万例 HZ 病例。根据 HCRU 的两个来源,每个 HZ 患者的平均 kgCO2e 从 61.0 kgCO2e 到 97.6 kgCO2e 不等,各年龄组的数值从 50-59 岁患者的 40.9 kgCO2e 到年龄≥80 岁患者的 195.9 kgCO2e 不等。在年龄≥50 岁的美国人口中,每年与 HZ 相关的碳总量介于 67,000 至 107,000 吨 CO2e 之间。HZ 对美国碳足迹的影响导致大量温室气体(GHG)排放。假定不接种疫苗,随着人口老龄化,预计未来几年 HZ 的负担会增加,从而加剧其对温室气体排放的影响。(图 1)。
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引用次数: 0
Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines. 接种五价与六价疫苗后,白喉类毒素、破伤风类毒素、百日咳杆菌抗原和 b 型流感嗜血杆菌的抗体持续性。
IF 4.1 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-05-16 DOI: 10.1080/21645515.2024.2352909
Nasamon Wanlapakorn, Nasiri Sarawanangkoor, Donchida Srimuan, Thaksaporn Thatsanathorn, Thanunrat Thongmee, Yong Poovorawan

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

泰国自 1977 年起将全细胞百日咳 (wP) 疫苗纳入扩大免疫计划,并自 2001 年起将无细胞百日咳 (aP) 疫苗作为婴儿的可选疫苗。我们对一项临床试验(ClinicalTrials.gov NCT02408926)中的健康儿童进行了跟踪调查,在该试验中,儿童被随机分配接种五价疫苗(DTwP-HB-Hib)或六价疫苗(DTaP-IPV-HB-Hib),接种时间为初种系列(2、4 和 6 个月接种)和首次加强接种(18 个月)。两组儿童都在 4 岁时接种了百白破-IPV 作为第二次加强免疫。每年收集血样以评估 2 至 6 岁儿童对白喉类毒素 (DT)、破伤风类毒素 (TT) 和百日咳杆菌 (B. pertussis) 的抗体持久性,并在第二次加强免疫后 1 个月进行百白破-IPV 的免疫原性研究。对乙型流感嗜血杆菌(Hib)的抗体持续性进行了跟踪,直至 3 岁。共有 105 名接种过六价疫苗的儿童和 91 名接种过五价疫苗的儿童完成了这项研究。五价组和六价组在接种百白破-IPV 第二次加强免疫后,对 DT、TT 和百日咳杆菌抗原的抗体水平都有所提高。强化后 1 个月时,所有儿童的抗 DT 和抗 TT IgG 都达到了血清保护浓度。六价组抗百日咳毒素 IgG 明显更高(调整后 p = .023),而五价组抗百日咳毒素 IgG 明显更高(调整后 p = .023)。
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引用次数: 0
A highly neutralizing human monoclonal antibody targeting a novel linear epitope on staphylococcal enterotoxin B. 针对葡萄球菌肠毒素 B 上的新型线性表位的高中和性人类单克隆抗体。
IF 4.1 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-06-10 DOI: 10.1080/21645515.2024.2360338
Hongyin Fan, Liqun Zhao, Weiwei Wang, Feng Yu, Haiming Jing, Yun Yang, Xiaoli Zhang, Zhuo Zhao, Qiang Gou, Weijun Zhang, Quanming Zou, Jinyong Zhang, Hao Zeng

Staphylococcal Enterotoxin B (SEB), produced by Staphylococcus aureus (S. aureus), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of S. aureus, there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen S. aureus vaccine. X-ray crystallography studies revealed that Hm0487 exhibits high affinity for a linear B cell epitope in SEB (SEB138-147), which is located distantly from the site involved in the formation of the MHC-SEB-TCR ternary complex. Furthermore, in vitro studies demonstrated that Hm0487 significantly impacts the interaction of SEB with both receptors and the binding to immune cells, probably due to an allosteric effect on SEB rather than competing with receptors for binding sites. Moreover, both in vitro and in vivo studies validated that Hm0487 displayed efficient neutralizing efficacy in models of lethal shock and sepsis induced by either SEB or bacterial challenge. Our findings unveil an alternative mechanism for neutralizing the pathogenesis of SEB by Hm0487, and this antibody provides a novel strategy for mitigating both SEB-induced toxicity and S. aureus infection.

由金黄色葡萄球菌(S. aureus)产生的葡萄球菌肠毒素 B(SEB)是一种强大的超级抗原,与 MHC-II 和 TCR 结合后会诱发严重的免疫紊乱和中毒性休克综合征(TSS)。尽管它对金黄色葡萄球菌的发病机制有重大影响,但目前还没有特定的治疗干预措施来对抗这种毒素的作用机制。在这项研究中,我们利用从参加金黄色葡萄球菌五抗原疫苗 I 期临床试验的志愿者体内分离出的 PBMCs,通过单细胞测序鉴定出了一种特异性靶向 SEB 的人类单克隆抗体(名为 Hm0487)。X 射线晶体学研究显示,Hm0487 对 SEB 中的线性 B 细胞表位(SEB138-147)具有高亲和力,该表位与 MHC-SEB-TCR 三元复合物的形成位点相距甚远。此外,体外研究表明,Hm0487 会显著影响 SEB 与两种受体的相互作用以及与免疫细胞的结合,这可能是由于对 SEB 的异构效应,而不是与受体竞争结合位点。此外,体外和体内研究都验证了 Hm0487 在 SEB 或细菌挑战诱导的致死性休克和败血症模型中显示出高效的中和效力。我们的研究结果揭示了Hm0487中和SEB发病机制的另一种机制,这种抗体为减轻SEB诱导的毒性和金黄色葡萄球菌感染提供了一种新策略。
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引用次数: 0
Ex vivo observation of Pythium insidiosum-antigen treated neutrophils on three Pythium insidiosum strains isolated from vascular pythiosis patients. 体内观察经脓疱疮抗原处理的中性粒细胞对从血管脓疱病患者体内分离出的三种脓疱疮菌株的影响。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-05 DOI: 10.1080/21645515.2024.2304372
Sadeep Medhasi, Apichaya Sriwarom, Nitipong Permpalung, Pattama Torvorapanit, Rongpong Plongla, Ariya Chindamporn, Navaporn Worasilchai

The mechanisms of Pythium insidiosum-antigen (PIA) immunotherapy activating a patient's immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti-P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 (p < .05). Neutrophils stimulated with 0.01, 0.1, 1, and 10 µg/ml PIA exhibited significantly lower zoospore viability than PIA-unstimulated neutrophils for strain 2 (p < .05). IL-8 can be used as a biomarker for monitoring vascular pythiosis cases treated with the PIA vaccine. Also, anti-P. insidiosum activity of PIA-stimulated neutrophils was probably due to the disruption of cellular activity in zoospores rather than the mechanisms based on the formation of NETs.

脓疱疮抗原(PIA)免疫疗法激活患者免疫系统的机制尚不清楚。我们评估了血管脓疱病病例在感染脓疱疮期间和接种脓疱疮疫苗后的白细胞介素-8(IL-8)血清水平。此外,我们还研究了从血管脓毒血症患者体内分离出的 3 株 P. insidiosum,用不同浓度的 PIA 在体外刺激中性粒细胞的抗 P. insidiosum 活性。使用 ELISA 技术评估了 IL-8 血清水平。我们使用 MTT 试验评估了 PIA 刺激的中性粒细胞对动物孢子活力的影响,通过显微镜观察了中性粒细胞胞外捕获器(NET)的形成,并使用 PicoGreen dsDNA 定量分析法测定了从血管脓疱病患者体内分离出的 3 株 P. insidiosum 的双链 DNA(dsDNA)水平。在血管性脓疱病存活病例组中,IL-8的血清水平从接种PIA初期到末期逐渐降低。与未受 PIA 刺激的中性粒细胞相比,受 0.01 µg/ml PIA 刺激的中性粒细胞可显著降低 1 号菌株和 3 号菌株的虫孢子活力(p p P. insidiosum),PIA 刺激的中性粒细胞的活性可能是由于破坏了虫孢子的细胞活性,而不是基于 NET 的形成机制。
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ACS Applied Energy Materials
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