Soubal Jean-Pierre, Lugo Aloyma, Santana-Mederos Darielys, Garrido Raine, Rodriguez-Noda Laura M, Perez-Nicado Rocmira, Soroa-Millan Yamilka, Fariñas Mildrey, Valdés-Balbín Yury, García-Rivera Dagmar, Rivera Daniel G, Vérez-Bencomo Vicente
Finlay Institute of Vaccines, 200 and 21 Street, Havana, 11600, Cuba.
Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Zapata & G, Havana, 10400, Cuba.
Chembiochem. 2025 Jan 2;26(1):e202400684. doi: 10.1002/cbic.202400684. Epub 2024 Nov 6.
Streptococcus pneumoniae is a bacterial pathogen causing diseases as severe as pneumonia, sepsis and meningitis. Most commercial pneumococcal conjugate vaccines contain the 7F serotype, which is epidemiologically relevant and highly invasive. This serotype contains an O-acetyl group at the internal L-rhamnose of its polysaccharide repeating unit. Herein we report on the role of the O-acetyl moiety of 7F polysaccharide in both antigen recognition and the induction of a protective antibody response against 7F. Fully and partially de-O-acetylated 7F polysaccharides were chemically prepared and compared with the O-acetylated counterpart in their antigenicity and immunogenicity of their tetanus toxoid glycoconjugates. These comparative studies showed a slight but consistent decrease in the antigenicity for the fully de-O-acetylated polysaccharide, but not for the partly de-O-acetylated variant. The glycoconjugates derived from the O-acetylated and the fully de-O-acetylated polysaccharides had similar sizes and polysaccharide-to-protein ratio, and all proved both to be immunogenic and induce opsonophagocytic responses in mice. Nevertheless, the immune response elicited by the O-acetylated glycoconjugate was better in both quantity and quality, proving that the O-acetyl group is not strictly necessary but also not irrelevant for the antigenicity and immunogenicity of the 7F serotype polysaccharide and its glycoconjugates.
肺炎链球菌是一种可引发如肺炎、败血症和脑膜炎等严重疾病的病原菌。大多数商业化的肺炎球菌结合疫苗包含7F血清型,该血清型在流行病学上具有相关性且具有高度侵袭性。此血清型在其多糖重复单元的内部L-鼠李糖上含有一个O-乙酰基。在此我们报告7F多糖的O-乙酰部分在抗原识别以及诱导针对7F的保护性抗体反应中的作用。通过化学方法制备了完全和部分脱O-乙酰化的7F多糖,并将它们与O-乙酰化的对应物在破伤风类毒素糖缀合物的抗原性和免疫原性方面进行了比较。这些比较研究表明,完全脱O-乙酰化的多糖的抗原性略有但持续下降,而部分脱O-乙酰化的变体则没有。源自O-乙酰化和完全脱O-乙酰化多糖的糖缀合物具有相似的大小和多糖与蛋白质的比例,并且所有这些都被证明在小鼠中具有免疫原性并能诱导调理吞噬反应。然而,O-乙酰化糖缀合物引发的免疫反应在数量和质量上都更好,这证明O-乙酰基对于7F血清型多糖及其糖缀合物的抗原性和免疫原性并非严格必要,但也并非无关紧要。