Raso Maria Michelina, Gasperini Gianmarco, Alfini Renzo, Schiavo Fabiola, Aruta Maria Grazia, Carducci Martina, Forgione Maria Concetta, Martini Silvia, Cescutti Paola, Necchi Francesca, Micoli Francesca
GSK Vaccines Institute for Global Health (GVGH) S.r.l., via Fiorentina 1, 53100 Siena, Italy.
Department of Life Science, University of Trieste, Building C11, via L. Giorgieri 1, 34127 Trieste, Italy.
Vaccines (Basel). 2020 Apr 3;8(2):160. doi: 10.3390/vaccines8020160.
infections are one of the top causes of diarrhea throughout the world, with being predominant in developing countries. Currently, no vaccines are widely available and increasing levels of multidrug-resistance make a high priority for vaccine development. The serotype-specific O-antigen moiety of lipopolysaccharide has been recognized as a key target for protective immunity, and many O-antigen based candidate vaccines are in development. Recently, the Generalized Modules for Membrane Antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for O-antigen delivery. Here, these two technologies are compared for a vaccine against serotype 6. Genetic strategies for GMMA production, conjugation approaches for linkage of the O-antigen to CRM carrier protein, and a large panel of analytical methods for full vaccine characterization have been put in place. In a head-to-head immunogenicity study in mice, GMMA induced higher anti-O-antigen IgG than glycoconjugate administered without Alhydrogel. When formulated on Alhydrogel, GMMA and glycoconjugate elicited similar levels of persistent anti-O-antigen IgG with bactericidal activity. Glycoconjugates are a well-established bacterial vaccine approach, but can be costly, particularly when multicomponent preparations are required. With similar immunogenicity and a simpler manufacturing process, GMMA are a promising strategy for the development of a vaccine against .
感染是全球腹泻的主要原因之一，在发展中国家更为普遍。目前，尚无广泛可用的疫苗，而且多重耐药性水平不断上升，使得疫苗开发成为当务之急。[细菌名称]脂多糖的血清型特异性O抗原部分已被确认为保护性免疫的关键靶点，许多基于O抗原的候选疫苗正在研发中。最近，膜抗原通用模块（GMMA）技术已被提议作为一种替代传统糖缀合物疫苗来递送O抗原的方法。在此，对这两种针对[细菌名称]血清型6的疫苗技术进行了比较。已经建立了GMMA生产的基因策略、O抗原与CRM载体蛋白连接的缀合方法以及用于全面疫苗表征的大量分析方法。在一项小鼠的直接免疫原性研究中，GMMA诱导产生的抗O抗原IgG高于未添加氢氧化铝佐剂的糖缀合物。当与氢氧化铝佐剂一起配制时，GMMA和糖缀合物引发了具有杀菌活性的相似水平的持续性抗O抗原IgG。糖缀合物是一种成熟的细菌疫苗方法，但成本可能很高，特别是在需要多组分制剂时。由于具有相似的免疫原性和更简单的生产工艺，GMMA是开发针对[细菌名称]疫苗的一种有前景的策略。
