Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
IHRC Inc., Contractor to Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
mBio. 2021 May 18;12(3):e00855-21. doi: 10.1128/mBio.00855-21.
Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different ( = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period. The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities.
2015 年至 2016 年,在美国两所大学开展了针对 B 群脑膜炎奈瑟菌引起的疾病暴发的反应以及在一所未发生暴发和应对活动的大学进行了带菌者评估。两所大学所有符合条件的学生都接种了 B 群脑膜炎奈瑟菌因子 H 结合蛋白疫苗(MenB-FHbp);一所大学的 5.2%(181/3509)学生接种了 MenB-4C。从 7001 名参与者的 8905 份咽拭子中获得了 1514 份脑膜炎奈瑟菌带菌者分离物。使用全基因组测序数据来了解 MenB-FHbp 对带菌者的影响以及抗原遗传多样性和分布。在已知接种状态的 1422 个分离物中(726 个来自 MenB-FHbp 疫苗接种者,42 个来自 MenB-4C 疫苗接种者,654 个来自未接种者),1406 个(98.9%)携带完整的 基因(716 个来自 MenB-FHbp 疫苗接种者)。在 726 个来自 MenB-FHbp 疫苗接种者的分离物中,250 个(34.4%)携带可能被 MenB-FHbp 覆盖的 FHbp 肽。在 MenB-FHbp 疫苗接种者和未接种者中,分别检测到 122/1422(8.6%)和 112/1422(7.9%)的分离物为 B 群基因。在 MenB-FHbp 疫苗接种者和未接种者之间,FHbp 亚家族和肽分布没有统计学差异。在多次样本采集过程中,161 名 MenB-FHbp 重复带菌者中有 18 名(11.2%)获得了含有一个或多个新疫苗抗原肽的新菌株,这与未接种的重复带菌者(30 名中的 1 名;3.3%)没有统计学差异( = 0.3176)。我们的研究结果表明,脑膜炎奈瑟菌(MenB)疫苗对带菌者的影响不是由于缺失完整的 基因所致;在研究期间,MenB-FHbp 并未影响抗原遗传多样性和分布。脑膜炎 B 群(MenB)疫苗对带菌者的影响尚不完全清楚。我们使用全基因组测序数据评估了三所美国大学接种和未接种疫苗的学生中 1514 份脑膜炎奈瑟菌带菌者分离物中 MenB 疫苗抗原(特别是 FHbp)的多样性和分布,其中两所大学在脑膜炎奈瑟菌疾病暴发后进行了 MenB-FHbp 大规模疫苗接种运动。从参与者中恢复的大多数带菌者分离物都携带有完整的 基因,其中约一半是从 MenB-FHbp 疫苗接种者中恢复的。从接种者和未接种者中恢复的带菌者分离物中疫苗抗原肽的分布相似,并且从重复带菌者中恢复的几乎所有菌株都保留了相同的疫苗抗原谱,这表明在这些大学的带菌者人群中,疫苗的选择压力不大。