3型肺炎链球菌在对感染高度易感的小鼠中逃避了PCV13诱导的免疫反应。
Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to Infection.
作者信息
Oliveira Giuliana S, Rivera Johanna, Rodrigues Tasson C, Carneiro Giovanna B, Ribeiro Orlando G, Miyaji Eliane N, Pirofski Liise-Anne, Oliveira Maria Leonor S
机构信息
Bacteriology Laboratory, Instituto Butantan, São Paulo, Brazil.
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, New York, Bronx, USA.
出版信息
Immun Inflamm Dis. 2024 Dec;12(12):e70062. doi: 10.1002/iid3.70062.
BACKGROUND
Streptococcus pneumoniae (pneumococcus) is a common cause of respiratory and invasive infections in humans. PCV13, a pneumococcal conjugate vaccine used globally, is highly effective against diseases caused by pneumococcal serotypes included in its formulation. However, one of them, the serotype 3 (ST3) is still being relatively commonly isolated from patients, suggesting an escape from vaccine-induced immunity. The thick capsule produced by ST3 facilitates bacterial evasion from the immune system. Additionally, host immune responses may influence the outcome of ST3 infection. Here we evaluated the influence of inflammation in the adaptive immune responses and protection induced by PCV13 against ST3, using two outbred mice lines that were phenotypically selected for high (AIRmax) and low (AIRmin) inflammatory responses.
METHODS
AIRmin and AIRmax mice were immunized with PCV13. Inbred BALB/c mice were used as reference for vaccine efficacy. Induction of IgG against polysaccharides (PS) from pneumococcal serotype 1 (ST1) and ST3 were evaluated by ELISA. Protection was tested against invasive infections with ST1 and ST3 pneumococcal strains. Sera were compared by IgG binding to pneumococcal surface, induction of pneumococcal agglutination and opsonophagocytosis. The phagocytic capacity of mice-derived neutrophils was also evaluated.
RESULTS
Immunization of AIRmin, AIRmax and BALB/c mice with PCV13 induced IgG against PS from ST1 and ST3 pneumococci. Despite vaccination, AIRmin mice were not protected against fatal infection with ST3. Sera from AIRmin mice immunized with PCV13 presented lower levels of anti-PS3 IgG, with reduced capacity to bind to pneumococcal surface. Reduced capacity to induce opsonophagocytosis of ST3 pneumococci in vitro was also observed. Conversely, PCV13 protected AIRmin mice against fatal infection with ST1 and this correlated with the capacity of the sera to induce ST1 opsonophagocytosis.
CONCLUSIONS
Our results show that both host and bacterial features can influence the outcome of protection induced by PCV13 against ST3 pneumococcal infection.
背景
肺炎链球菌（肺炎球菌）是人类呼吸道感染和侵袭性感染的常见病因。13价肺炎球菌结合疫苗（PCV13）在全球范围内使用，对其配方中包含的肺炎球菌血清型引起的疾病高度有效。然而，其中血清型3（ST3）仍相对常见于患者中分离出，提示其逃避了疫苗诱导的免疫。ST3产生的厚荚膜有助于细菌逃避免疫系统。此外，宿主免疫反应可能影响ST3感染的结果。在这里，我们使用两种经表型选择具有高（AIRmax）和低（AIRmin）炎症反应的远交系小鼠，评估炎症对PCV13诱导的针对ST3的适应性免疫反应和保护作用的影响。
方法
用PCV13免疫AIRmin和AIRmax小鼠。近交BALB/c小鼠用作疫苗效力的参考。通过酶联免疫吸附测定（ELISA）评估针对肺炎球菌血清型1（ST1）和ST3多糖（PS）的IgG诱导情况。测试针对ST1和ST3肺炎球菌菌株侵袭性感染的保护作用。通过IgG与肺炎球菌表面结合、肺炎球菌凝集诱导和调理吞噬作用比较血清。还评估了小鼠来源中性粒细胞的吞噬能力。
结果
用PCV13免疫AIRmin、AIRmax和BALB/c小鼠可诱导针对ST1和ST3肺炎球菌PS的IgG。尽管接种了疫苗，但AIRmin小鼠未受到针对ST3致命感染的保护。用PCV13免疫的AIRmin小鼠血清中抗PS3 IgG水平较低，与肺炎球菌表面结合能力降低。体外诱导ST3肺炎球菌调理吞噬作用的能力也降低。相反，PCV13保护AIRmin小鼠免受ST1致命感染，这与血清诱导ST1调理吞噬作用的能力相关。
结论
我们的结果表明，宿主和细菌特征均可影响PCV13诱导的针对ST3肺炎球菌感染的保护结果。
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