Berstad A K, Holst J, Møgster B, Haugen I L, Haneberg B
Department of Vaccinology, National Institute of Public Health, Oslo, Norway.
Vaccine. 1997 Aug-Sep;15(12-13):1473-8. doi: 10.1016/s0264-410x(97)00064-9.
The immunogenicity of formaldehyde-inactivated Bordetella pertussis (Bp) delivered by the intranasal or colonic-rectal routes in BALB/c mice was studied by immunization four times at weekly intervals with Bp alone, or with Bp mixed with cholera toxin (CT) as a mucosal adjuvant. Mice given Bp subcutaneously, and untreated mice served as controls. Antibody responses in serum, saliva, bronchoalveolar lavage (BAL) fluids and extracts of faeces were measured by enzyme-linked immunosorbent assay. Nasal immunizations with Bp alone induced high levels of IgG antibodies to Bp in serum and BAL fluids, as well as IgA antibodies in serum, saliva, BAL fluids and extracts of faeces. The IgA responses were significantly reduced, and the IgG responses were not increased, when CT was given intranasally together with Bp. However, CT increased the IgA responses to Bp in faeces when both antigens were given rectally, while rectal administration of Bp alone did not induce significant serum or secretory antibody responses. However, when mixed with Bp, the CT itself induced antibodies to CT in serum and samples representing secretions after both nasal and rectal administrations. Thus, Bp is strongly immunogenic when applied intranasally, but not when presented into the intestinal lumen via the rectal route. It appears that CT, which is known to be a mucosal adjuvant and which in itself is a strong mucosal immunogen, will inhibit the immune responses of other strong immunogens when applied on the nasal mucosa.
通过每周免疫一次，连续四次单独给予百日咳博德特氏菌（Bp）或给予与霍乱毒素（CT）混合作为黏膜佐剂的Bp，研究了经鼻内或结肠-直肠途径给予甲醛灭活的Bp在BALB/c小鼠中的免疫原性。皮下给予Bp的小鼠和未处理的小鼠作为对照。通过酶联免疫吸附测定法测量血清、唾液、支气管肺泡灌洗（BAL）液和粪便提取物中的抗体反应。单独经鼻免疫Bp可诱导血清和BAL液中针对Bp的高水平IgG抗体，以及血清、唾液、BAL液和粪便提取物中的IgA抗体。当CT与Bp一起经鼻给予时，IgA反应显著降低，而IgG反应未增加。然而，当两种抗原经直肠给予时，CT增加了粪便中对Bp的IgA反应，而单独直肠给予Bp未诱导显著的血清或分泌性抗体反应。然而，当与Bp混合时，CT本身在经鼻和直肠给药后的血清和代表分泌物的样本中诱导了针对CT的抗体。因此，Bp经鼻应用时具有强烈的免疫原性，但经直肠途径进入肠腔时则不然。已知CT是一种黏膜佐剂，其本身也是一种强大的黏膜免疫原，当应用于鼻黏膜时，它会抑制其他强免疫原的免疫反应。
