tetano
Editor, Senior Moderator
Curr Pharm Biotechnol
. 2020 Nov 4.
doi: 10.2174/1389201021666201104145006. Online ahead of print.
Design, synthesis and primary immunologic evaluation of M2e-CRM197 conjugate as a universal influenza vaccine candidate
Lu Xu[SUP] 1 [/SUP], Chun Zhang[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Rong Yu[SUP] 1 [/SUP], Zhiguo Su[SUP] 2 [/SUP]
Affiliations
Abstract
Background: Influenza is a contagious respiratory illness caused by acute infection of influenza viruses, among which influenza A virus causes epidemic seasonal infection nearly every year. Along with unpredictability of evolving influenza A virus and time-consuming vaccine development cycles, novel universal influenza vaccine designed to induce broadly cross-reactive immune responses against frequently mutant influenza A virus strains are greatly urgent.
Objective: The aim of this study was to synthesize a novel vaccine through the dual-site specific conjugation of the constant epitope of 23 amino acids (M2e) of influenza A virus with highly immunogenic carrier protein of cross-reacting material (CRM197) under denaturation, and evaluate its primary immunogenicity in mice.
Methods: The antigen (M2e) and the carrier protein (CRM197) were linked with different type of hetero-functionalized linkers, α-maleimide-ε-hydrazide polyethylene glycol 2k (MAL-PEG-HZ) and N-β-maleimidopropionic acid hydrazide (BMPH) separately. The immunogenicity of the M2e-CRM197 conjugates with different type of linkers was evaluated in mice, and the M2e-specific total IgG and IgG-isotypes were determined by ELSIA.
Results: Immunogenicity study revealed that anti-M2e antibody could be induced by the conjugate products, M2e-PEGCRM197 and M2e-BMPH-CRM197, were approximately 30 and 90-fold higher than that of M2e group. In addition, the antiM2e antibody level induced by M2e-PEG-CRM197 conjugate was three times higher than that of M2e-BMPH-CRM197 conjugate, and the former could simultaneously activate both cellar and humoral immune responses.
Conclusions: The M2e-CRM197 conjugated vaccines we synthesized in this study are highly immunogenic compared with M2e alone. Besides, evidences were presented here indicated that the hydrophilic, non-immunogenic and biocompatible chain of the cross-linker might be a better choice for development of conjugate vaccine.
Keywords: Influenza; anti-M2e antibody; conjugate vaccine; cross-reacting material (CRM197); ectodomain of matrix protein 2 (M2e); polyethylene glycol.
. 2020 Nov 4.
doi: 10.2174/1389201021666201104145006. Online ahead of print.
Design, synthesis and primary immunologic evaluation of M2e-CRM197 conjugate as a universal influenza vaccine candidate
Lu Xu[SUP] 1 [/SUP], Chun Zhang[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Rong Yu[SUP] 1 [/SUP], Zhiguo Su[SUP] 2 [/SUP]
Affiliations
- PMID: 33148152
- DOI: 10.2174/1389201021666201104145006
Abstract
Background: Influenza is a contagious respiratory illness caused by acute infection of influenza viruses, among which influenza A virus causes epidemic seasonal infection nearly every year. Along with unpredictability of evolving influenza A virus and time-consuming vaccine development cycles, novel universal influenza vaccine designed to induce broadly cross-reactive immune responses against frequently mutant influenza A virus strains are greatly urgent.
Objective: The aim of this study was to synthesize a novel vaccine through the dual-site specific conjugation of the constant epitope of 23 amino acids (M2e) of influenza A virus with highly immunogenic carrier protein of cross-reacting material (CRM197) under denaturation, and evaluate its primary immunogenicity in mice.
Methods: The antigen (M2e) and the carrier protein (CRM197) were linked with different type of hetero-functionalized linkers, α-maleimide-ε-hydrazide polyethylene glycol 2k (MAL-PEG-HZ) and N-β-maleimidopropionic acid hydrazide (BMPH) separately. The immunogenicity of the M2e-CRM197 conjugates with different type of linkers was evaluated in mice, and the M2e-specific total IgG and IgG-isotypes were determined by ELSIA.
Results: Immunogenicity study revealed that anti-M2e antibody could be induced by the conjugate products, M2e-PEGCRM197 and M2e-BMPH-CRM197, were approximately 30 and 90-fold higher than that of M2e group. In addition, the antiM2e antibody level induced by M2e-PEG-CRM197 conjugate was three times higher than that of M2e-BMPH-CRM197 conjugate, and the former could simultaneously activate both cellar and humoral immune responses.
Conclusions: The M2e-CRM197 conjugated vaccines we synthesized in this study are highly immunogenic compared with M2e alone. Besides, evidences were presented here indicated that the hydrophilic, non-immunogenic and biocompatible chain of the cross-linker might be a better choice for development of conjugate vaccine.
Keywords: Influenza; anti-M2e antibody; conjugate vaccine; cross-reacting material (CRM197); ectodomain of matrix protein 2 (M2e); polyethylene glycol.