tetano
Editor, Senior Moderator
Vaccines (Basel). 2019 Sep 18;7(3). pii: E117. doi: 10.3390/vaccines7030117.
[h=1]An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains.[/h] Sun W[SUP]1[/SUP], Zheng A[SUP]2[/SUP], Miller R[SUP]3[/SUP], Krammer F[SUP]4[/SUP], Palese P[SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. weina.sun@mssm.edu. 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. allen.zheng@icahn.mssm.edu. 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. robert.miller@mssm.edu. 4 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. florian.krammer@mssm.edu. 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. peter.palese@mssm.edu. 6 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. peter.palese@mssm.edu.
[h=3]Abstract[/h] Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation.
[h=4]KEYWORDS:[/h] ADCC; conserved epitopes; cross-protection; enhanced immunogenicity; immunodominance; universal influenza virus vaccine
PMID: 31540436 DOI: 10.3390/vaccines7030117
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[h=1]An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains.[/h] Sun W[SUP]1[/SUP], Zheng A[SUP]2[/SUP], Miller R[SUP]3[/SUP], Krammer F[SUP]4[/SUP], Palese P[SUP]5,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. weina.sun@mssm.edu. 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. allen.zheng@icahn.mssm.edu. 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. robert.miller@mssm.edu. 4 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. florian.krammer@mssm.edu. 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. peter.palese@mssm.edu. 6 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. peter.palese@mssm.edu.
[h=3]Abstract[/h] Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation.
[h=4]KEYWORDS:[/h] ADCC; conserved epitopes; cross-protection; enhanced immunogenicity; immunodominance; universal influenza virus vaccine
PMID: 31540436 DOI: 10.3390/vaccines7030117
Free full text