Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle wa...Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle was tested as influenza vaccine carrier by chemically conjugating a matrix protein 2 ectodomain(M2e)antigen peptide or/and the full-length hemagglutinin(HA)antigen on the outer surface of the AFt,with heterobifunctional sSMCC or SM(PEG)_(24) containing PEG chain as linkers.To each AFt nanoparticle,about 30-32 M2e or 1.8 HA antigen could be coupled.The AFt-(PEG)24-M2e,in which the M2e was coupled through SM(PEG)_(24) containing PEG chain,conferred higher protective efficacy in immunized mice than AFt-M2e did,but was less effective than AFt-(PEG)_(24)-HA.When both M2e and HA were coupled,the synthesized dual-antigen vaccine candidate AFt-(PEG)_(24)-M2e/HA elicited high level of M2e and HA antigen-specific antibodies and conferred 100%protection against lethal infection of homologous PR8 HI N1 virus strain and 70%protection against a heterologous A/FM/1/47(FM1,H1N1)strain,which was more effective than the M2e or HA single antigen vaccine candidates.The potential cross-protective effect of the dual-antigen vaccine was further demonstrated by significant specific hemagglutination inhibition(HAI)titers in serum of the immunized mice against three other heterologous viral strains including A/Singapore/GPl908/2015(IVR-180)H1N1,A/Anhui/1/2005 H5N1,and A/Hong Kong H3N2.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21821005,31970872).
文摘Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle was tested as influenza vaccine carrier by chemically conjugating a matrix protein 2 ectodomain(M2e)antigen peptide or/and the full-length hemagglutinin(HA)antigen on the outer surface of the AFt,with heterobifunctional sSMCC or SM(PEG)_(24) containing PEG chain as linkers.To each AFt nanoparticle,about 30-32 M2e or 1.8 HA antigen could be coupled.The AFt-(PEG)24-M2e,in which the M2e was coupled through SM(PEG)_(24) containing PEG chain,conferred higher protective efficacy in immunized mice than AFt-M2e did,but was less effective than AFt-(PEG)_(24)-HA.When both M2e and HA were coupled,the synthesized dual-antigen vaccine candidate AFt-(PEG)_(24)-M2e/HA elicited high level of M2e and HA antigen-specific antibodies and conferred 100%protection against lethal infection of homologous PR8 HI N1 virus strain and 70%protection against a heterologous A/FM/1/47(FM1,H1N1)strain,which was more effective than the M2e or HA single antigen vaccine candidates.The potential cross-protective effect of the dual-antigen vaccine was further demonstrated by significant specific hemagglutination inhibition(HAI)titers in serum of the immunized mice against three other heterologous viral strains including A/Singapore/GPl908/2015(IVR-180)H1N1,A/Anhui/1/2005 H5N1,and A/Hong Kong H3N2.
