The influenza A(H1 N1)pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A(H1 N1)pdm09-infected patient case hospitalized for two month...The influenza A(H1 N1)pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A(H1 N1)pdm09-infected patient case hospitalized for two months in Guangdong(from December 14,2019 to February 15,2020).This isolate,named A/Guangdong/LCF/2019(LCF/19),was genetically sequenced,rescued by reverse genetics,and phylogenetically analyzed in the context of other relevant pdm09 isolates.Compared with earlier isolates,this pdm09 virus’s genetic sequence contains four substitutions,S186 P,T188 I,D190 A,and Q192 E,of the hemagglutinin(HA)segment at position 186–192(H3 numbering)in the epitope Sb,and two of which are located at the 190-helix.Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in2018.To characterize the pathogenicity of this novel substitution motif,a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued.Kinetic growth data revealed that the reassortant viruses,including the LCF/2019 with the PTIAAQE substitution,propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney(MDCK)cells.The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018,suggesting that old vaccines might not effectively protect people from infection.Due to the difference in the selection of vaccine strains,people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.展开更多
This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eig...This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82074311)the General Project of Guangzhou Medical University(Grant No.SKLRD-MS201908)the Yunnan Provincial Science and Technology Department(Grant No.202005AF150043)。
文摘The influenza A(H1 N1)pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years.Here,we analyzed a clinical influenza A(H1 N1)pdm09-infected patient case hospitalized for two months in Guangdong(from December 14,2019 to February 15,2020).This isolate,named A/Guangdong/LCF/2019(LCF/19),was genetically sequenced,rescued by reverse genetics,and phylogenetically analyzed in the context of other relevant pdm09 isolates.Compared with earlier isolates,this pdm09 virus’s genetic sequence contains four substitutions,S186 P,T188 I,D190 A,and Q192 E,of the hemagglutinin(HA)segment at position 186–192(H3 numbering)in the epitope Sb,and two of which are located at the 190-helix.Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in2018.To characterize the pathogenicity of this novel substitution motif,a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued.Kinetic growth data revealed that the reassortant viruses,including the LCF/2019 with the PTIAAQE substitution,propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney(MDCK)cells.The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018,suggesting that old vaccines might not effectively protect people from infection.Due to the difference in the selection of vaccine strains,people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.
文摘This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.
