Haneberg B, Dalseg R, Wedege E, Høiby E A, Haugen I L, Oftung F, Andersen S R, Naess L M, Aase A, Michaelsen T E, Holst J
Department of Vaccinology, National Institute of Public Health, Oslo, Norway.
Infect Immun. 1998 Apr;66(4):1334-41. doi: 10.1128/IAI.66.4.1334-1341.1998.
A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later. Each nasal dose consisted of 250 microg of protein, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers. All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months. Intramuscular immunizations did not lead to antibody responses in the secretions. Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody responses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose. The pattern of serum antibody specificities against the different OMV components after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc. Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.
一种由B群脑膜炎奈瑟菌外膜囊泡（OMV）组成的鼻用疫苗，以滴鼻剂或鼻喷雾剂的形式，每周给12名志愿者接种一次，共接种四次，5个月后接种第五剂。每剂鼻用疫苗含250微克蛋白质，相当于给另外11名志愿者每隔6周接种两次的肌内剂量的10倍。所有接种鼻用疫苗的个体在鼻分泌物中均产生了针对OMV的免疫球蛋白A（IgA）抗体反应，8人产生了唾液IgA抗体，且持续至少5个月。肌内免疫未导致分泌物中产生抗体反应。5名经鼻免疫的志愿者血清IgG抗体有适度增加，而10人对肌内疫苗反应强烈。鼻用疫苗两至三剂后，血清和分泌型抗体反应均达到最大值，第五剂无明显加强作用。经鼻免疫后血清抗体针对不同OMV成分的特异性模式与肌内疫苗基本相似。鼻用疫苗组分别有5名和8名接种者血清杀菌效价持续升高，分别针对表达低水平和高水平外膜蛋白Opc的同源脑膜炎球菌疫苗株。我们的结果表明，脑膜炎球菌OMV作为鼻用疫苗时，具备引发全身及局部黏膜免疫反应所需的结构。尽管血清抗体水平不如肌内接种疫苗后明显，但显著的杀菌活性表明，一种非增殖性鼻用疫苗可能诱导出功能质量高的抗体。
