tetano
Editor, Senior Moderator
Front Immunol. 2018 Oct 12;9:2350. doi: 10.3389/fimmu.2018.02350. eCollection 2018.
[h=1]Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice.[/h] van der Lubbe JEM[SUP]1[/SUP], Verspuij JWA[SUP]1[/SUP], Huizingh J[SUP]1[/SUP], Schmit-Tillemans SPR[SUP]1[/SUP], Tolboom JTBM[SUP]1[/SUP], Dekking LEHA[SUP]1[/SUP], Kwaks T[SUP]1[/SUP], Brandenburg B[SUP]1[/SUP], Meijberg W[SUP]1[/SUP], Zahn RC[SUP]1[/SUP], Roozendaal R[SUP]1[/SUP], Kuipers H[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Seasonal influenza vaccines are updated almost annually to match the antigenic drift in influenza hemagglutinin (HA) surface glycoprotein. A new HA stem-based antigen, the so-called "mini-HA," was recently shown to induce cross-protective antibodies. However, cross-reactive antibodies targeting the HA stem can also be found in mice and humans after administration of seasonal vaccine. This has raised the question whether in similar conditions such a mini-HA would be able to show an increased breadth of protection over immunization with full length (FL) HA. We show in mice that in a direct comparison to H1 FL HA, using the same immunization regimen, dosing and adjuvant, a group 1 mini-HA has a higher protective efficacy against group 1 influenza virus challenges not homologous to the H1 FL HA. Although both antigens induce a similar breadth of HA subtype binding, mini-HA immunization induces significantly more HA stem-specific antibodies correlating with survival. In addition, both mini-HA and H1 FL HA immunization induce influenza neutralizing antibodies while mini-HA induces significantly higher levels of mFcγRIII activation, involved in Fc-mediated antibody effector functions. In agreement with previous findings, this confirms that more than one mechanism contributes to protection against influenza. Together our results further warrant the development of a universal influenza vaccine based on the HA stem region.
[h=4]KEYWORDS:[/h] antibodies; hemagglutinin stem immunogen; influenza; mouse influenza challenge models; universal influenza vaccine
PMID: 30369928 PMCID: PMC6194913 DOI: 10.3389/fimmu.2018.02350
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[h=1]Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice.[/h] van der Lubbe JEM[SUP]1[/SUP], Verspuij JWA[SUP]1[/SUP], Huizingh J[SUP]1[/SUP], Schmit-Tillemans SPR[SUP]1[/SUP], Tolboom JTBM[SUP]1[/SUP], Dekking LEHA[SUP]1[/SUP], Kwaks T[SUP]1[/SUP], Brandenburg B[SUP]1[/SUP], Meijberg W[SUP]1[/SUP], Zahn RC[SUP]1[/SUP], Roozendaal R[SUP]1[/SUP], Kuipers H[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Seasonal influenza vaccines are updated almost annually to match the antigenic drift in influenza hemagglutinin (HA) surface glycoprotein. A new HA stem-based antigen, the so-called "mini-HA," was recently shown to induce cross-protective antibodies. However, cross-reactive antibodies targeting the HA stem can also be found in mice and humans after administration of seasonal vaccine. This has raised the question whether in similar conditions such a mini-HA would be able to show an increased breadth of protection over immunization with full length (FL) HA. We show in mice that in a direct comparison to H1 FL HA, using the same immunization regimen, dosing and adjuvant, a group 1 mini-HA has a higher protective efficacy against group 1 influenza virus challenges not homologous to the H1 FL HA. Although both antigens induce a similar breadth of HA subtype binding, mini-HA immunization induces significantly more HA stem-specific antibodies correlating with survival. In addition, both mini-HA and H1 FL HA immunization induce influenza neutralizing antibodies while mini-HA induces significantly higher levels of mFcγRIII activation, involved in Fc-mediated antibody effector functions. In agreement with previous findings, this confirms that more than one mechanism contributes to protection against influenza. Together our results further warrant the development of a universal influenza vaccine based on the HA stem region.
[h=4]KEYWORDS:[/h] antibodies; hemagglutinin stem immunogen; influenza; mouse influenza challenge models; universal influenza vaccine
PMID: 30369928 PMCID: PMC6194913 DOI: 10.3389/fimmu.2018.02350
Free full text