Reddy M V N Janardhan, Devarakonda Yogeshwar, Burki Rajendar, Syal Kirtimaan
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Telangana 500078, India.
Research & Development, Biological E Limited, Shameerpet, Hyderabad 500078, India.
ACS Omega. 2025 Aug 18;10(33):37862-37873. doi: 10.1021/acsomega.5c04889. eCollection 2025 Aug 26.
Invasive pneumococcal disease presents a threat to humankind, predominantly affecting children and the elderly. Despite the availability of high-valency pneumococcal polysaccharide vaccine of PPSV23 (PNEUMOVAX 23) and conjugate vaccines such as VAXNEUVANCE and PREVNAR 20, nonvaccine serotypes continue to contribute to higher mortality rates. The characterization of nonvaccine serotypes is becoming increasingly crucial considering an increase in their prevalence. In this study, biochemical characteristics, immunological properties, and critical quality attributes of the capsular polysaccharide isolated from prevalent nonvaccine serotype 38 (American type 71) have been examined. Advanced analytical techniques, including multiangle light scattering (MALS), ion chromatography, and dynamic light scattering in addition to conventional biochemical methods and SLOTBLOT analysis, were employed. We observed that serotype 38 capsular polysaccharide has a molar mass of 768 kDa with a distribution of 1.5 (±4.5%) and a -average radius of gyration ( ) of 90 nm. The polysaccharide composition included galactose, -acetylglucosamine, and galacturonic acid, with a distinct peak indicating the presence of the amino acid serine. The near-zero zeta potential measurements indicated that the polysaccharide is either zwitterionic or uncharged. Serotype 38 polysaccharide exhibited immunological cross-reactivity with serotype 5 and serotype 1 polyclonal sera, likely due to a shared epitope region containing a keto sugar component (Sugp) in their repeating units, along with net charge properties similar to serotype 1. These findings revealed novel characteristics of the serotype 38 polysaccharide, including its amino acid composition and net charge, which may contribute to the development of new therapeutics and effective vaccines.
侵袭性肺炎球菌疾病对人类构成威胁，主要影响儿童和老年人。尽管有高价肺炎球菌多糖疫苗PPSV23（纽莫法23）以及如沛儿新等结合疫苗，但非疫苗血清型仍导致较高的死亡率。鉴于其流行率的增加，对非疫苗血清型的特征进行鉴定变得越来越关键。在本研究中，对从流行的非疫苗血清型38（美国71型）分离出的荚膜多糖的生化特性、免疫特性和关键质量属性进行了研究。除了传统的生化方法和斑点杂交分析外，还采用了先进的分析技术，包括多角度光散射（MALS）、离子色谱和动态光散射。我们观察到血清型38荚膜多糖的摩尔质量为768 kDa，分布系数为1.5（±4.5%），平均旋转半径（ ）为90 nm。多糖成分包括半乳糖、N-乙酰葡糖胺和半乳糖醛酸，有一个明显的峰表明存在氨基酸丝氨酸。接近零的zeta电位测量表明该多糖要么是两性离子型要么是不带电的。血清型38多糖与血清型5和血清型1的多克隆血清表现出免疫交叉反应性，这可能是由于它们的重复单元中存在一个包含酮糖成分（Sugp）的共同表位区域，以及与血清型1相似的净电荷特性。这些发现揭示了血清型38多糖的新特性，包括其氨基酸组成和净电荷，这可能有助于开发新的治疗方法和有效的疫苗。
