Lamond Nicole, Zimmerman Lindsey, Wang Yihui, Maldonado Villeda Jonatan, Bjarnason Asgeir, Jóhannsdóttir Hekla Bryndís, Skoff Tami H, Tondella Maria-Lucia, Weigand Michael R, Hariri Susan, Merkel Tod
Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Star-Oddi, Gardabaer, Iceland.
mSphere. 2025 Jul 21:e0031025. doi: 10.1128/msphere.00310-25.
Pertussis is a respiratory disease caused by the bacterium . Acellular pertussis (aP) vaccines replaced more reactogenic whole-cell pertussis (wP) vaccines in the United States in the 1990s. Despite high rates of vaccination, a slow but consistent increase in the number of U.S. pertussis cases was observed starting in the 1980s that accelerated following the introduction of aP vaccines. Most aP vaccines contain pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN), and some contain fimbriae (FIM 2/3). Countries that transitioned into aP vaccines have observed increasing rates of pertactin-negative (PRN) clinical isolates, exceeding 85% in some countries. This outcome suggests does not require PRN, and immune responses against PRN may impact circulation. With the high prevalence of PRN strains circulating in the United States, we sought to identify an acceptable PRN strain for use in baboon challenge studies and controlled human infection model (CHIM) studies. Baboons were challenged with the PRN-positive (PRN) strain D420 or one of three PRN strains selected to represent the genetic diversity of strains circulating in the United States. Despite comparable levels of colonization between the animals infected with the PRN strains and D420, there was variability between the three PRN strains with respect to virulence, and two of the three strains appeared reduced in one or more measures of virulence. These findings suggest that some PRN clinical isolates may be less virulent than D420 and suggest care should be taken when selecting strains for baboon and CHIM studies.IMPORTANCEWith the increased circulation of PRN strains in countries using acellular pertussis (aP) vaccines, understanding the epidemiology and pathogenesis of PRN strains is critical. Our results suggest that virulence varies between circulating PRN strains, with some strains appearing to be less virulent than PRN strains. These results tell us that care should be taken when selecting PRN pertussis strains for baboon and CHIM studies. Our results may also support the continued use of PRN in aP vaccines. If PRN strains are less virulent and induce less severe disease than PRN strains, maintaining vaccine selective pressure against PRN strains may be beneficial.
百日咳是一种由细菌引起的呼吸道疾病。20世纪90年代，无细胞百日咳（aP）疫苗在美国取代了反应原性更强的全细胞百日咳（wP）疫苗。尽管疫苗接种率很高，但自20世纪80年代起，美国百日咳病例数开始缓慢但持续增加，在引入aP疫苗后加速上升。大多数aP疫苗含有百日咳毒素（PT）、丝状血凝素（FHA）和百日咳杆菌黏附素（PRN），有些还含有菌毛（FIM 2/3）。已过渡到使用aP疫苗的国家观察到百日咳杆菌黏附素阴性（PRN）临床分离株的比例不断上升，在一些国家超过了85%。这一结果表明 不需要PRN，且针对PRN的免疫反应可能会影响 传播。鉴于美国PRN菌株的高流行率，我们试图鉴定一种可接受的PRN菌株，用于狒狒攻毒研究和人体感染对照模型（CHIM）研究。用PRN阳性（PRN）菌株D420或选择的三种PRN菌株之一对狒狒进行攻毒，所选菌株代表在美国流行的 菌株的基因多样性。尽管感染PRN菌株的动物与感染D420的动物之间的定植水平相当，但三种PRN菌株在毒力方面存在差异，三种菌株中的两种在一项或多项毒力指标上表现出降低。这些发现表明，一些PRN临床分离株的毒力可能低于D420，并表明在为狒狒和CHIM研究选择菌株时应谨慎。重要性随着使用无细胞百日咳（aP）疫苗的国家中PRN菌株传播的增加，了解PRN菌株的流行病学和发病机制至关重要。我们的结果表明，流行的PRN菌株之间毒力不同，一些菌株的毒力似乎低于PRN菌株。这些结果告诉我们，在为狒狒和CHIM研究选择PRN百日咳菌株时应谨慎。我们的结果也可能支持在aP疫苗中继续使用PRN。如果PRN菌株的毒力低于PRN菌株且引起的疾病较轻，维持针对PRN菌株的疫苗选择压力可能是有益的。 （注：原文中部分关键细菌名称未完整给出，翻译时保留原文格式）
