Rubinstein L J, García-Ojeda P A, Michon F, Jennings H J, Stein K E
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Infect Immun. 1998 Nov;66(11):5450-6. doi: 10.1128/IAI.66.11.5450-5456.1998.
The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny. The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases. We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization. The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1. A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine. The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals. Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate. The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone. These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting.
许多致病细菌的多糖（PS）荚膜在婴幼儿中是较差的免疫原，这是由于个体发育过程中对PS抗原的反应延迟所致。b型流感嗜血杆菌多糖蛋白结合疫苗已被证明在该年龄组中有效，这促使许多研究人员积极开发针对其他疾病的结合疫苗。我们在此描述了几种小鼠品系对与破伤风类毒素结合的C群脑膜炎奈瑟菌荚膜PS（MCPS-TT）的反应，以及在BALB/c小鼠中的相同反应，以此作为结合疫苗免疫的免疫后果模型。使用结合疫苗会导致对MCPS产生反应时所引发的免疫球蛋白类型发生转变，从免疫球蛋白M（IgM）和IgG3转变为主要是IgG1。即使在对MCPS本身反应较差的小鼠品系中，也能看到对MCPS-TT的反应，这强调了在选择疫苗的小鼠模型时进行品系调查的重要性。IgG1抗体滴度的显著增加伴随着这些动物血清杀菌活性的大幅提高。用结合疫苗进行初次免疫的动物在再次用MCPS或结合疫苗免疫后表现出加强反应。对MCPS产生增强的IgG1抗MCPS反应的能力可以仅通过来自用MCPS-TT进行初次免疫的小鼠的B细胞转移给过继受体，而不能通过用MCPS单独进行初次免疫的小鼠的B细胞转移。这些数据表明，在BALB/c小鼠中，单次用MCPS-TT免疫足以诱导向IgG1的转变，并产生不需要T细胞进行加强的记忆B细胞群体。
