Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens

International Journal of Molecular Sciences

Francesca Necchi¹  Elena Palmieri¹  Alessandra Acquaviva¹  Maria Grazia Aruta¹  Roberta Di Benedetto¹  Carlo Giannelli¹  Martina Carducci¹  Allan Saul¹  Renzo Alfini¹  Luisa Lanzilao¹  Francesca Micoli¹ 

[1] GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy;

关键词: conjugation chemistry;    GMMA;    OMV;    carrier protein;    vaccine;    glycoconjugate;   

DOI  :  10.3390/ijms221910180

来源: DOAJ

【 摘 要 】

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.

【 授权许可】

Unknown