Nishat Sharmeen, Hossain Md Kamal, Valentin Geraud, Hossain Farzana, Gamage Shanika, Wall Katherine A, Andreana Peter R
Department of Chemistry, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh.
Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
Vaccines (Basel). 2024 Dec 6;12(12):1375. doi: 10.3390/vaccines12121375.
BACKGROUND/OBJECTIVES: The MHCII-dependent, CD4+ T-cell zwitterionic polysaccharide PS A1 has been investigated as a promising carrier for vaccine development because it can induce an MHCII-dependent CD4+ response towards a variety of tumor-associated carbohydrate antigens (TACAs). However, PS A1 cannot elicit cytotoxic T lymphocytes through MHCI, which may or may not hamper its potential clinical use in cancer, infectious and viral vaccine development. This paper addresses PS A1 MHCI independence through the introduction of an MHCI epitope, the poliovirus (PV) peptide, to establish an MHCI- and MHCII-dependent vaccine.
We synthesized a glycopeptide construct targeting the Thomsen-nouveau TACA (Tn-PV-PS A1) and a control Tn-PV peptide. C57BL/6 mice were immunized with both constructs, and the resulting T-cells were extracted from spleens.
Through cell proliferation assays, we show that Tn-PV-PS A1 elicits a robust CD4+ and CD8+ immune response. The resulting cytotoxic T lymphocytes are specific towards Tn-PV and trigger cell lysis of Tn-expressing EL4 cells.
This study confirms PV-PS A1 as a robust MHCI- and MHCII-dependent carrier. This is the first report of MHCI dependence in a zwitterionic polysaccharide.
背景/目的：依赖MHCII的CD4+ T细胞两性离子多糖PSA1已被研究作为一种有前景的疫苗开发载体，因为它可以诱导针对多种肿瘤相关碳水化合物抗原（TACA）的依赖MHCII的CD4+反应。然而，PSA1不能通过MHC I引发细胞毒性T淋巴细胞，这可能会也可能不会妨碍其在癌症、传染病和病毒疫苗开发中的潜在临床应用。本文通过引入MHC I表位脊髓灰质炎病毒（PV）肽来解决PSA1对MHC I的独立性问题，以建立一种依赖MHC I和MHCII的疫苗。
我们合成了一种靶向汤姆森-诺沃TACA（Tn-PV-PSA1）的糖肽构建体和一个对照Tn-PV肽。用这两种构建体免疫C57BL/6小鼠，并从脾脏中提取产生的T细胞。
通过细胞增殖试验，我们表明Tn-PV-PSA1引发了强大的CD4+和CD8+免疫反应。产生的细胞毒性T淋巴细胞对Tn-PV具有特异性，并触发表达Tn的EL4细胞的细胞裂解。
本研究证实PV-PSA1是一种强大的依赖MHC I和MHCII的载体。这是关于两性离子多糖中MHC I依赖性的首次报道。
