GSK Vaccines Institute for Global Health (GVGH) s.r.l, Via Fiorentina 1, 53100 Siena, Italy.
Department of Life Sciences, University of Trieste, Via L. Giorgieri 1, Bdg C11, 34127 Trieste, Italy.
Int J Mol Sci. 2021 Jan 28;22(3):1309. doi: 10.3390/ijms22031309.
Recently, generalized modules for membrane antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for O-antigen delivery. Saccharide length is a well-known parameter that can impact the immune response induced by glycoconjugates both in terms of magnitude and quality. However, the criticality of O-antigen length on the immune response induced by GMMA-based vaccines has not been fully elucidated. Here, and GMMA-producing strains were further mutated in order to display homogeneous polysaccharide populations of different sizes on a GMMA surface. Resulting GMMA were compared in mice immunization studies. Athymic nude mice were also used to investigate the involvement of T-cells in the immune response elicited. In contrast with what has been reported for traditional glycoconjugate vaccines and independent of the pathogen and the sugar structural characteristics, O-antigen length did not result in being a critical parameter for GMMA immunogenicity. This work supports the identification of critical quality attributes to optimize GMMA vaccine design and improve vaccine efficacy and gives insights on the nature of the immune response induced by GMMA.
最近，已经提出了通用膜抗原（GMMA）技术作为传统 O 抗原传递糖缀合物疫苗的替代方法。糖链长度是一个众所周知的参数，它可以影响糖缀合物诱导的免疫反应的强度和质量。然而，GMMA 疫苗诱导的免疫反应中 O 抗原长度的关键作用尚未得到充分阐明。在这里，为了在 GMMA 表面展示不同大小的均匀多糖群体，进一步突变了 和 产生 GMMA 的菌株。在小鼠免疫研究中比较了由此产生的 GMMA。还使用无胸腺裸鼠来研究 T 细胞在引发的免疫反应中的参与。与传统糖缀合物疫苗的报道相反，并且与病原体和糖结构特征无关，O 抗原长度并不是 GMMA 免疫原性的关键参数。这项工作支持确定关键质量属性以优化 GMMA 疫苗设计并提高疫苗效力，并提供了有关 GMMA 诱导的免疫反应性质的见解。
