Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
Vaccine Development Center at West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
Infect Immun. 2021 Feb 16;89(3). doi: 10.1128/IAI.00607-20.
colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased the bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant -specific IgG antibodies in both the serum and lung and increased numbers of anti- IgG-secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the i.n. vaccines correlated with protection, suggesting that long-term antibody responses can be protective.
定植于人体呼吸道黏膜，引发呼吸道内的免疫应答。个体一旦康复，便对该病原体产生长期免疫力。目前的无细胞百日咳（aP）疫苗无法诱导人类自然感染后观察到的长期免疫应答。在这项研究中，我们评估了鼻内（i.n.）百日咳疫苗在小鼠中的保护持久性。从感染中康复的小鼠作为对照组。小鼠用模拟疫苗（磷酸盐缓冲盐水[PBS]）、aP 或 aP 基础疫苗与以下佐剂之一联合免疫：明矾、几丁聚糖或纯化全葡聚糖颗粒（IRI-1501）。我们采用了两种研究设计：短期（在初次接种疫苗后 35 天挑战）和长期（在加强接种后 6 个月挑战）。短期研究表明，鼻内疫苗候选物的免疫接种降低了呼吸道中的细菌负担，减少了炎症标志物，并诱导了显著的血清和肺部抗体滴度。在长期研究中，细菌挑战的保护作用与短期挑战研究中观察到的结果一致。单独免疫百日咳抗原在两种模型中均具有惊人的保护作用；然而，明矾和 IRI-1501 佐剂在血清和肺部中诱导了显著的 IgG 抗体，并增加了骨髓中抗 IgG 分泌浆细胞的数量。我们的数据表明，i.n.疫苗诱导的体液反应与保护相关，表明长期抗体反应可以提供保护。
