Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens.
Animals
Antibodies, Bacterial
/ immunology
Antigens, Bacterial
/ immunology
Bacterial Proteins
/ chemistry
Bacterial Vaccines
/ biosynthesis
Extracellular Vesicles
/ immunology
Female
Lipopolysaccharides
/ immunology
Mice
Neisseria meningitidis
/ immunology
Plasmodium falciparum
/ immunology
Protozoan Proteins
/ chemistry
Protozoan Vaccines
/ biosynthesis
Salmonella typhimurium
/ immunology
Shigella sonnei
/ immunology
GMMA
OMV
carrier protein
conjugation chemistry
glycoconjugate
vaccine
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Sep 2021
22 Sep 2021
Historique:
received:
31
08
2021
revised:
17
09
2021
accepted:
17
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
28
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34638530
pii: ijms221910180
doi: 10.3390/ijms221910180
pmc: PMC8508390
pii:
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Bacterial Proteins
0
Bacterial Vaccines
0
Lipopolysaccharides
0
Pfs25 protein, Plasmodium falciparum
0
Protozoan Proteins
0
Protozoan Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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