Hvalbye B K, Aaberge I S, Løvik M, Haneberg B
Department of Vaccinology, National Institute of Public Health, 0403 Oslo, Norway.
Infect Immun. 1999 Sep;67(9):4320-5. doi: 10.1128/IAI.67.9.4320-4325.1999.
In order to study the mucosal and serum antibody response to polysaccharide-encapsulated bacteria in mice, a preparation of heat-inactivated Streptococcus pneumoniae type 4 was administered, with and without cholera toxin, at various mucosal sites. It appeared that intranasal immunization of nonanesthesized animals was superior to either oral, gastric, or colonic-rectal antigen delivery with regard to the induction of serum immunoglobulin G (IgG) and IgA, as well as saliva IgA antibodies specific for pneumococci. The marked IgA antibody response in feces after intranasal, but not after oral or gastric, immunization is suggestive of a cellular link between the nasal induction site and the distant mucosal effector sites. Intranasal immunization also induced antibodies in serum and in mucosal secretions against type-specific capsular polysaccharide. IgA and IgG antibody levels in pulmonary lavage fluids correlated well with saliva IgA and serum IgG antibodies, respectively. Antibody determinations in pulmonary secretions may therefore be redundant in some cases, and the number of experimental animals may be reduced accordingly. After intraperitoneal challenge with type 4 pneumococci, mice immunized intranasally were protected against both systemic infection and death, even without the use of cholera toxin as a mucosal adjuvant. Thus, an efficient intranasal vaccine against invasive pneumococcal disease may be based on a very simple formulation with whole killed pneumococci.
为了研究小鼠对多糖包裹细菌的黏膜和血清抗体反应，将热灭活的4型肺炎链球菌制剂在有或无霍乱毒素的情况下，经不同黏膜部位给药。结果显示，就诱导血清免疫球蛋白G（IgG）和IgA以及针对肺炎球菌的唾液IgA抗体而言，对未麻醉动物进行鼻内免疫优于口服、胃内或结肠直肠抗原递送。鼻内免疫后粪便中有明显的IgA抗体反应，而口服或胃内免疫后则没有，这表明鼻诱导部位与远处黏膜效应部位之间存在细胞联系。鼻内免疫还诱导血清和黏膜分泌物中产生针对型特异性荚膜多糖的抗体。肺灌洗液中的IgA和IgG抗体水平分别与唾液IgA和血清IgG抗体密切相关。因此，在某些情况下，检测肺分泌物中的抗体可能是多余的，相应地可以减少实验动物的数量。在用4型肺炎球菌进行腹腔攻击后，即使不使用霍乱毒素作为黏膜佐剂，经鼻内免疫的小鼠也能免受全身感染和死亡。因此，一种有效的抗侵袭性肺炎球菌疾病鼻内疫苗可能基于一种非常简单的全灭活肺炎球菌制剂。
