Quantifying the Breadth and Duration of Immunity Induced by Meningococcal B Vaccines

量化 B 型脑膜炎球菌疫苗诱导的免疫广度和持续时间

• 批准号: 10319592
• 负责人: Nicole Elaine Basta
• 金额: $ 50.86万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319592
• 关键词: Adult; Advisory Committees; Antibodies; Antigens; Biological Assay; Characteristics; Cohort Studies; Collection; Complement; Country; Development; Disease; Disease Outbreaks; Dose; Enrollment; Epidemiologic Methods; Health; Human; Immune response; Immunity; Immunization; Individual; Kinetics; Laboratories; Licensing; Licensure; Measures; Meningococcal vaccine; Methods; Morbidity - disease rate; Neisseria meningitidis; Policies; Prevention; Public Health; Qualifying; Recombinants; Recommendation; Research; Risk; Sampling; Serogroup B Neisseria meningitidis; Serology; Seroprevalences; Serum; Statistical Models; Students; Symptoms; Teenagers; Time; United States Food and Drug Administration; Universities; Vaccinated; Vaccination; Vaccinee; Vaccines; Voting; antibody test; bactericide; clinical epidemiology; cohort; college; comparison group; design; epidemiologic data; epidemiology study; follow-up; high risk; immunogenic; immunogenicity; improved; longitudinal, prospective study; mortality; new technology; novel; pathogenic bacteria; prevent; protective effect; response; tool; unvaccinated; vaccination strategy; vaccine response; vaccine-induced immunity; vaccinology; young adult

Project Summary/Abstract Meningococcal disease caused by the bacterial pathogen Neisseria meningitidis is responsible for significant morbidity and mortality worldwide. Preventing meningococcal disease is of particular public health importance because of the sudden onset of symptoms, rapid progression, and high case fatality even among previously healthy individuals. Serogroup B meningococcal (MenB) disease has caused outbreaks in multiple countries and the US, where several outbreaks occurred on college campuses in recent years. Teens and young adults are one of the groups at highest risk of invasive disease. In 2014 and 2015, two novel MenB vaccines, Bexsero (4CMenB, GSK) and Trumenba (rLP2086, Pfizer) were licensed in the US for 10-25 year olds. The extent to which these vaccines induce broadly protective, persistent immunity is unknown, limiting our ability to understand the kinetics of the immune response and to develop optimal vaccination strategies. In addition, no studies have evaluated these two vaccines using the same measures of immunity against the same disease-causing MenB isolates. We aim to advance the field of vaccinology and to improve efforts to prevent deadly cases of MenB disease by evaluating both the short-term and long-term immunogenicity of these MenB vaccines and by investigating the breadth of immunity induced against the diversity of MenB strains that cause disease. To achieve these aims, we will conduct clinical epidemiological research using a novel serum bank that we collected from teens and young adults during two of the first studies of Bexsero immunogenicity in the US, and we will extend the period of follow up among this unique cohort. In addition, we will use similar methods to enroll young adults into a prospective longitudinal study to evaluate Trumenba immunity. To evaluate immune responses, we will conduct serum bactericidal antibody assays using externally-derived human complement (hSBA) and a recently developed serum bactericidal antibody assay using intrinsic human complement (iSBA) to investigate how broadly immunogenic both vaccines are against a collection of dozens of MenB isolates and whether immunity persists long term. We will then develop statistical models to evaluate hSBA and iSBA responses and the relationship between these markers of functional immunity over time. We aim to rigorously and simultaneously evaluate Bexsero and Trumenba vaccine- induced immunity against the same panel of MenB strains. Meningococcal B vaccines are critical tools for the prevention of invasive meningococcal disease. Our research will combine new epidemiologic data, novel laboratory methods, and statistical models to generate urgently needed evidence that will increase our understanding of vaccine-induced immunity. Our results can be used to inform vaccination policy so that effective, targeted vaccination strategies can be designed and implemented.

项目摘要/摘要 由细菌病原体奈瑟氏菌引起的脑膜炎球菌疾病是重要的 全球发病率和死亡率。防止脑膜炎球菌疾病特别重要 由于症状突然发作，快速进展和高病例死亡，即使在以前 健康的个体。血清群B脑膜炎球菌（MENB）疾病在多个国家引起了爆发 和美国，近年来在大学校园发生了几次爆发。青少年 是侵入性疾病风险最高的群体之一。在2014年和2015年，两种新颖的MENB疫苗Bexsero （4CMENB，GSK）和Trumenba（RLP2086，辉瑞）在美国获得了10-25岁的年轻人的许可。范围 这些疫苗会引起广泛的保护性，持续的免疫力未知，限制了我们的能力 了解免疫反应的动力学并制定最佳疫苗接种策略。在 此外，没有研究使用相同的免疫措施评估了这两种疫苗 相同的引起疾病的MENB分离株。我们旨在推进疫苗学领域并改善努力 通过评估短期和长期免疫原性，以防止MENB疾病的致命病例 这些MENB疫苗并通过调查针对MENB多样性引起的免疫力广度 引起疾病的菌株。为了实现这些目标，我们将使用 在Bexsero的两项研究中，我们从青少年和年轻人那里收集的新型血清库 美国的免疫原性，我们将在此独特的队列中延长随访期。另外，我们 将使用类似的方法将年轻人纳入一项前瞻性纵向研究以评估Trumenba 免疫。为了评估免疫反应，我们将使用 外部人类补体（HSBA）和最近开发的血清杀菌抗体测定法 使用固有的人补体（ISBA）研究两种疫苗的广泛免疫原性反对A 收集了数十种MENB分离株以及免疫是否长期持续。然后，我们将开发统计 评估HSBA和ISBA响应以及功能标记之间的关系的模型 随着时间的推移免疫力。我们的目标是严格，同时评估Bexsero和Trumenba疫苗 诱导对同一MENB菌株的免疫力。脑膜炎球菌B疫苗是关键工具 预防侵入性脑膜炎球菌疾病。我们的研究将结合新的流行病学数据，新颖 实验室方法和统计模型以产生急需的证据，以增加我们的 了解疫苗诱导的免疫力。我们的结果可用于通知疫苗接种政策，以便 可以设计和实施有效的，有针对性的疫苗接种策略。

项目成果

What drives willingness to receive a new vaccine that prevents an emerging infectious disease? A discrete choice experiment among university students in Uganda.

• DOI: 10.1371/journal.pone.0268063
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Pneumococcal vaccination uptake and missed opportunities for vaccination among Canadian adults: A cross-sectional analysis of the Canadian Longitudinal Study on Aging (CLSA).

• DOI: 10.1371/journal.pone.0275923
• 发表时间: 2022
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Sulis, Giorgia;Rodrigue, Valerie;Wolfson, Christina;McMillan, Jacqueline M.;Kirkland, Susan A.;Andrew, Melissa K.;Basta, Nicole E.
• 通讯作者: Basta, Nicole E.

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study.

• DOI: 10.1136/bmj.n1943
• 发表时间: 2021-08-20
• 期刊: BMJ (Clinical research ed.)
• 作者: Chung H;He S;Nasreen S;Sundaram ME;Buchan SA;Wilson SE;Chen B;Calzavara A;Fell DB;Austin PC;Wilson K;Schwartz KL;Brown KA;Gubbay JB;Basta NE;Mahmud SM;Righolt CH;Svenson LW;MacDonald SE;Janjua NZ;Tadrous M;Kwong JC;Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators
• 通讯作者: Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators

Influenza vaccination uptake among Canadian adults before and during the COVID-19 pandemic: An analysis of the Canadian Longitudinal study on Aging (CLSA).

• DOI: 10.1016/j.vaccine.2021.11.088
• 发表时间: 2022-01-24
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Sulis G;Basta NE;Wolfson C;Kirkland SA;McMillan J;Griffith LE;Raina P;Canadian Longitudinal Study on Aging (CLSA) Team
• 通讯作者: Canadian Longitudinal Study on Aging (CLSA) Team

Validity of university students' self-reported vaccination status after a meningococcal B outbreak.

• DOI: 10.1080/07448481.2020.1772270
• 发表时间: 2022-04
• 期刊: Journal of American college health : J of ACH
• 作者: Ulrich AK;McKearnan SB;Lammert S;Wolfson J;Pletcher J;Halloran ME;Basta NE
• 通讯作者: Basta NE