tetano
Editor, Senior Moderator
Hum Gene Ther. 2018 Jul 31. doi: 10.1089/hum.2018.102. [Epub ahead of print]
[h=1]A Synthetic Micro-Consensus DNA Vaccine Generates Comprehensive Influenza-A H3N2 Immunity and Protects Mice Against Lethal Challenge by Multiple H3N2 Viruses.[/h] Elliott S[SUP]1[/SUP], Keaton AA[SUP]2[/SUP], Chu JD[SUP]3[/SUP], Reed CC[SUP]4[/SUP], Garman B[SUP]5[/SUP], Patel A[SUP]6[/SUP], Yan J[SUP]7[/SUP], Broderick KE[SUP]8[/SUP], Weiner D[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza-A H3N2 viruses circulate globally, leading to substantial morbidity and mortality. Commercially-available, antigen-matched influenza vaccines must be updated frequently to match dynamic sequence variability in immune epitopes, especially within viral hemagglutinin H3. In an effort to create comprehensive immune responses against H3N2, we developed four micro-consensus antigens designed to mimic the sequence and antigenic diversity of H3. Synthetic plasmid DNA constructs were constructed to express each micro-consensus immunogen, and combined into a multi-antigen DNA vaccine cocktail, pH3HA. Facilitated delivery of pH3HA via intramuscular electroporation in mice induced comprehensive, potent humoral responses against diverse seasonal H3N2 viruses that circulated between 1968 and the present. Vaccination with pH3HA also induced an antigen-specific cellular cytokine response. Mice immunized with pH3HA were protected against lethal challenge using two distinct H3N2 viruses, highlighting the heterologous protection afforded by synthetic micro-consensus immunogens. These findings warrant further study of the DNA vaccine micro-consensus platform for broad protection against influenza viruses.
PMID: 30062926 DOI: 10.1089/hum.2018.102
[h=1]A Synthetic Micro-Consensus DNA Vaccine Generates Comprehensive Influenza-A H3N2 Immunity and Protects Mice Against Lethal Challenge by Multiple H3N2 Viruses.[/h] Elliott S[SUP]1[/SUP], Keaton AA[SUP]2[/SUP], Chu JD[SUP]3[/SUP], Reed CC[SUP]4[/SUP], Garman B[SUP]5[/SUP], Patel A[SUP]6[/SUP], Yan J[SUP]7[/SUP], Broderick KE[SUP]8[/SUP], Weiner D[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza-A H3N2 viruses circulate globally, leading to substantial morbidity and mortality. Commercially-available, antigen-matched influenza vaccines must be updated frequently to match dynamic sequence variability in immune epitopes, especially within viral hemagglutinin H3. In an effort to create comprehensive immune responses against H3N2, we developed four micro-consensus antigens designed to mimic the sequence and antigenic diversity of H3. Synthetic plasmid DNA constructs were constructed to express each micro-consensus immunogen, and combined into a multi-antigen DNA vaccine cocktail, pH3HA. Facilitated delivery of pH3HA via intramuscular electroporation in mice induced comprehensive, potent humoral responses against diverse seasonal H3N2 viruses that circulated between 1968 and the present. Vaccination with pH3HA also induced an antigen-specific cellular cytokine response. Mice immunized with pH3HA were protected against lethal challenge using two distinct H3N2 viruses, highlighting the heterologous protection afforded by synthetic micro-consensus immunogens. These findings warrant further study of the DNA vaccine micro-consensus platform for broad protection against influenza viruses.
PMID: 30062926 DOI: 10.1089/hum.2018.102