Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02350/full |
| _version_ | 1819062995864518656 |
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| author | Joan E. M. van der Lubbe Johan W. A. Verspuij Jeroen Huizingh Sonja P. R. Schmit-Tillemans Jeroen T. B. M. Tolboom Liesbeth E. H. A. Dekking Ted Kwaks Börries Brandenburg Wim Meijberg Roland C. Zahn Ramon Roozendaal Harmjan Kuipers |
| author_facet | Joan E. M. van der Lubbe Johan W. A. Verspuij Jeroen Huizingh Sonja P. R. Schmit-Tillemans Jeroen T. B. M. Tolboom Liesbeth E. H. A. Dekking Ted Kwaks Börries Brandenburg Wim Meijberg Roland C. Zahn Ramon Roozendaal Harmjan Kuipers |
| author_sort | Joan E. M. van der Lubbe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T15:07:39Z |
| format | Article |
| id | doaj.art-322bfb8a4d904d03bb6ca95c5abe3554 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T15:07:39Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-322bfb8a4d904d03bb6ca95c5abe35542022-12-21T18:59:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02350396899Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in MiceJoan E. M. van der LubbeJohan W. A. VerspuijJeroen HuizinghSonja P. R. Schmit-TillemansJeroen T. B. M. TolboomLiesbeth E. H. A. DekkingTed KwaksBörries BrandenburgWim MeijbergRoland C. ZahnRamon RoozendaalHarmjan KuipersSeasonal 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02350/fulluniversal influenza vaccinehemagglutinin stem immunogeninfluenzamouse influenza challenge modelsantibodies |
| spellingShingle | Joan E. M. van der Lubbe Johan W. A. Verspuij Jeroen Huizingh Sonja P. R. Schmit-Tillemans Jeroen T. B. M. Tolboom Liesbeth E. H. A. Dekking Ted Kwaks Börries Brandenburg Wim Meijberg Roland C. Zahn Ramon Roozendaal Harmjan Kuipers Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice Frontiers in Immunology universal influenza vaccine hemagglutinin stem immunogen influenza mouse influenza challenge models antibodies |
| title | Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice |
| title_full | Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice |
| title_fullStr | Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice |
| title_full_unstemmed | Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice |
| title_short | Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice |
| title_sort | mini ha is superior to full length hemagglutinin immunization in inducing stem specific antibodies and protection against group 1 influenza virus challenges in mice |
| topic | universal influenza vaccine hemagglutinin stem immunogen influenza mouse influenza challenge models antibodies |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02350/full |
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