García-Ojeda Pablo A, Hardy Sharon, Kozlowski Steven, Stein Kathryn E, Feavers Ian M
Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drugs Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Infect Immun. 2004 Jun;72(6):3451-60. doi: 10.1128/IAI.72.6.3451-3460.2004.
Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis group C PS (MCPS), are characterized as being thymus independent and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin derivative CRM197, elicit thymus-dependent responses. The present study developed a surface plasmon resonance approach to evaluate Ab responses to MCPS conjugate vaccines, including either O-acetylated (OAc+) or de-O-acetylated (OAc-) forms of the PS. The results were generally consistent with those obtained by enzyme-linked immunosorbent assay and showed that sera from mice immunized with conjugate vaccines contain Abs that bind more effectively to OAc+ and OAc- MCPS than sera from mice immunized with fixed bacteria. The data suggest a critical shared or overlapping epitope recognized by all the conjugate vaccine immune sera and strategies for assessing polyclonal Ab avidity.
对多糖(PS)的抗体(Ab)反应,如针对脑膜炎奈瑟菌C群多糖(MCPS)的反应,其特点是不依赖胸腺,并且在克隆型和同种型表达方面受到限制。与蛋白质偶联的PS,例如与破伤风类毒素或白喉毒素衍生物CRM197偶联的MCPS,会引发依赖胸腺的反应。本研究开发了一种表面等离子体共振方法,以评估对MCPS结合疫苗的Ab反应,包括PS的O - 乙酰化(OAc +)或去O - 乙酰化(OAc -)形式。结果与通过酶联免疫吸附测定获得的结果总体一致,表明用结合疫苗免疫的小鼠血清中含有的抗体比用固定细菌免疫的小鼠血清中的抗体更有效地结合OAc +和OAc - MCPS。数据表明存在一个被所有结合疫苗免疫血清识别的关键共同或重叠表位,以及评估多克隆抗体亲和力的策略。