Saunders N B, Shoemaker D R, Brandt B L, Moran E E, Larsen T, Zollinger W D
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Infect Immun. 1999 Jan;67(1):113-9. doi: 10.1128/IAI.67.1.113-119.1999.
Colonization of the human nasopharyngeal region by Neisseria meningitidis is believed to lead to natural immunity. Although the presence of bactericidal antibody in serum has been correlated with immunity to meningococcal disease, mucosal immunity at the portal of entry may also play an important role. This study was undertaken to examine in mice the possibility of safely using native outer membrane vesicles (NOMV) not exposed to detergent as an intranasal (i.n.) vaccine. The mucosal and systemic responses of mice to intranasal and intraperitoneal (i.p.) vaccination with NOMV were compared over a range of doses from 0.1 to 20 microgram. Intranasal vaccination of mice with NOMV induced a strong systemic bactericidal antibody response, as well as a strong local immunoglobulin A immune response in the lung as determined by assay of lung lavage fluid by enzyme-linked immunosorbent assay and lung antibody secreting cells by enzyme-linked immunospot assay. However, 8- to 10-fold-higher doses of NOMV were required i.n. compared to i.p. to elicit an equivalent bactericidal antibody response in serum. Some NOMV vaccine was aspirated into the lungs of mice during i.n. immunization and resulted in an acute inflammatory response that peaked at 1 to 2 days postimmunization and was cleared by day 7. These results indicate that i.n. delivery of meningococcal NOMV in mice is highly effective in eliciting the production of both a mucosal immune response and a systemic bactericidal antibody response.
脑膜炎奈瑟菌在人类鼻咽部的定植被认为可产生自然免疫力。尽管血清中杀菌抗体的存在与对脑膜炎球菌病的免疫力相关，但在病原体进入门户处的黏膜免疫也可能发挥重要作用。本研究旨在检测在小鼠中安全使用未接触去污剂的天然外膜囊泡（NOMV）作为鼻内（i.n.）疫苗的可能性。比较了小鼠在0.1至20微克范围内不同剂量鼻内和腹腔内（i.p.）接种NOMV后的黏膜和全身反应。通过酶联免疫吸附测定法检测肺灌洗液以及通过酶联免疫斑点测定法检测肺抗体分泌细胞，结果表明，小鼠鼻内接种NOMV可诱导强烈的全身杀菌抗体反应以及肺部强烈的局部免疫球蛋白A免疫反应。然而，与腹腔内接种相比，鼻内接种需要高8至10倍剂量的NOMV才能在血清中引发等效的杀菌抗体反应。在鼻内免疫期间，一些NOMV疫苗被吸入小鼠肺部，导致急性炎症反应，在免疫后1至2天达到峰值，并在第7天清除。这些结果表明，在小鼠中鼻内递送脑膜炎球菌NOMV在引发黏膜免疫反应和全身杀菌抗体反应方面非常有效。
