IMMUNOGENICITY IN ANIMALS OF A POLYSACCHARIDE-PROTEIN CONJUGATE VACCINE AGAINST TYPE-III GROUP-B STREPTOCOCCUS
IMMUNOGENICITY IN ANIMALS OF A POLYSACCHARIDE-PROTEIN CONJUGATE VACCINE AGAINST TYPE-III GROUP-B STREPTOCOCCUS
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DOI：
10.1172/jci114858
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发表时间：
1990-11-01
影响因子：
15.9
通讯作者：
JENNINGS, HJ
中科院分区：
文献类型：
--
作者：
WESSELS, MR;PAOLETTI, LC;JENNINGS, HJ
II型B族伊氏链球菌的天然荚膜多糖仅在60%的非免疫人类受试者中产生特异性抗体应答。为了增强这种多糖的免疫原性，我们将III型多糖与破伤风类毒素偶联。在偶联之前，通过受控的高碘酸盐氧化在多糖上引入醛基，导致多糖的25%的唾液酸残基转化为唾液酸的8-碳类似物5-乙酰氨基-3，5-二脱氧-D-半乳糖基辛酮糖酸的残基。破伤风类毒素通过还原胺化，经由部分氧化的唾液酸残基上存在的游离醛基与多糖缀合。用缀合物疫苗免疫的兔产生与天然III型B组链球菌多糖反应的IgG抗体（3/3只兔），而用未缀合的III型多糖免疫的兔没有应答（0/3只兔）。来自接受缀合物疫苗的动物的血清调理III型B族链球菌以用于人外周血白细胞的吞噬杀伤，并保护小鼠免受活的III型B族链球菌的致死攻击。结果表明，这种与载体蛋白缀合的方法可能是改善III型B族链球菌多糖在人类受试者中的免疫原性的有用策略。
The native capsular polysaccharide of type II group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human subjects.