tetano
Editor, Senior Moderator
J Virol. 2017 Feb 8. pii: JVI.02052-16. doi: 10.1128/JVI.02052-16. [Epub ahead of print]
[h=1]A bivalent heterologous DNA-virus-like particles prime-boost vaccine elicits broad protection against both groups 1 and 2 influenza A viruses.[/h] Jiang W[SUP]1[/SUP], Wang S[SUP]1,[/SUP][SUP]2[/SUP], Chen H[SUP]3[/SUP], Ren H[SUP]1[/SUP], Huang X[SUP]1[/SUP], Wang G[SUP]1[/SUP], Chen Z[SUP]4[/SUP], Chen L[SUP]5[/SUP], Chen Z[SUP]3[/SUP], Zhou P[SUP]6,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus there is a critical need for developing so-called "universal" vaccines that protect against all influenza viruses. In the present study we developed a bivalent heterologous DNA-virus-like particles (VLP) prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge of group 1 (H1, H5 and H9) and group 2 (H3 and H7) viruses with 94% aggregate survival. To determine immune correlates of protection, we performed passive immunizations and in vitro assays. We show that this vaccine elicited antibody responses that bound HA from group 1 (H1, H2, H5, H6, H8, H9, H11 and H12) and group 2 (H3, H4, H7, H10, H14 and H15) and neutralized homologous and intrasubtypic H5 and H7 and heterosubtypic H1 viruses and HA-specific CD4 and CD8 T cell responses. As a result, passive immunization with immune sera fully protected mice from H5, H7 and H1 challenge; whereas with both immune sera and T cells completely survived from heterosubtypic H3 and H9 challenge. Thus it appears that neutralizing antibodies alone fully protect homologous and intrasubtypic H5 and H7; neutralizing and binding antibodies are sufficient to protect heterosubtypic H1; but against heterosubtypic H3 and H9 binding antibodies and T cells are required for complete survival. We believe that this vaccine regimen could potentially be a candidate for "universal" influenza vaccine.IMPORTANCE Influenza virus infection is global health problem. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Because of this, there is an urgent need to develop so-called "universal" influenza vaccines that can protect against both current and future influenza strains. In the present study we developed a bivalent heterologous prime-boost vaccine strategy. We show that this bivalent vaccine regimen elicited broad binding and neutralizing antibody and T cell responses that conferred broad protection against diverse challenge viruses in mice, suggesting that this bivalent prime-boost strategy could practically be a candidate for "universal" influenza vaccine.
Copyright ? 2017 American Society for Microbiology.
PMID: 28179535 DOI: 10.1128/JVI.02052-16
[PubMed - as supplied by publisher]
[h=1]A bivalent heterologous DNA-virus-like particles prime-boost vaccine elicits broad protection against both groups 1 and 2 influenza A viruses.[/h] Jiang W[SUP]1[/SUP], Wang S[SUP]1,[/SUP][SUP]2[/SUP], Chen H[SUP]3[/SUP], Ren H[SUP]1[/SUP], Huang X[SUP]1[/SUP], Wang G[SUP]1[/SUP], Chen Z[SUP]4[/SUP], Chen L[SUP]5[/SUP], Chen Z[SUP]3[/SUP], Zhou P[SUP]6,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus there is a critical need for developing so-called "universal" vaccines that protect against all influenza viruses. In the present study we developed a bivalent heterologous DNA-virus-like particles (VLP) prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge of group 1 (H1, H5 and H9) and group 2 (H3 and H7) viruses with 94% aggregate survival. To determine immune correlates of protection, we performed passive immunizations and in vitro assays. We show that this vaccine elicited antibody responses that bound HA from group 1 (H1, H2, H5, H6, H8, H9, H11 and H12) and group 2 (H3, H4, H7, H10, H14 and H15) and neutralized homologous and intrasubtypic H5 and H7 and heterosubtypic H1 viruses and HA-specific CD4 and CD8 T cell responses. As a result, passive immunization with immune sera fully protected mice from H5, H7 and H1 challenge; whereas with both immune sera and T cells completely survived from heterosubtypic H3 and H9 challenge. Thus it appears that neutralizing antibodies alone fully protect homologous and intrasubtypic H5 and H7; neutralizing and binding antibodies are sufficient to protect heterosubtypic H1; but against heterosubtypic H3 and H9 binding antibodies and T cells are required for complete survival. We believe that this vaccine regimen could potentially be a candidate for "universal" influenza vaccine.IMPORTANCE Influenza virus infection is global health problem. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. But they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Because of this, there is an urgent need to develop so-called "universal" influenza vaccines that can protect against both current and future influenza strains. In the present study we developed a bivalent heterologous prime-boost vaccine strategy. We show that this bivalent vaccine regimen elicited broad binding and neutralizing antibody and T cell responses that conferred broad protection against diverse challenge viruses in mice, suggesting that this bivalent prime-boost strategy could practically be a candidate for "universal" influenza vaccine.
Copyright ? 2017 American Society for Microbiology.
PMID: 28179535 DOI: 10.1128/JVI.02052-16
[PubMed - as supplied by publisher]