Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice.

Joan E M Van Der Lubbe,Börries Brandenburg,Jeroen T B M Tolboom,Harmjan Kuipers,Johan W A Verspuij,Ramon Roozendaal,Roland C Zahn,Wim Meijberg,Liesbeth E H A Dekking,Ted Kwaks,Jeroen Huizingh,Sonja P R Schmit-Tillemans

doi:10.3389/fimmu.2018.02350

Joan E M Van Der Lubbe, Börries Brandenburg + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2018.02350

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Abstract

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.

Highlights

Influenza is a major global health problem causing serious morbidity, mortality, and substantial productivity loss each year
To compare the crossprotective efficacy of mini-HA immunization to H1 full length (FL) HA we selected two influenza strains with genetically distant HAs; H1N1 A/PuertoRico/8/1934 is a strain heterologous to the H1 FL HA A/Brisbane/59/2007 (87% HA amino acid identity) and H5N1 A/HongKong/156/97 is a strain genetically more distant and heterosubtypic to the H1 FL HA used for immunization (63% HA aa identity to H1 FL HA A/Brisbane/59/2007)
Cross-protection against influenza induced by immunization with the mini-HA or a seasonal vaccine previously has shown to be mediated by the humoral immune response in various studies [10, 23, 24, 26]

Summary

Introduction

Influenza is a major global health problem causing serious morbidity, mortality, and substantial productivity loss each year. The most cost-effective strategy to prevent influenza is by vaccination [1, 2]. Current seasonal vaccines are often effective, a mismatch between circulating virus strains and the strains included in the vaccine occasionally reduces vaccine efficacy [3]. Seasonal vaccines have limited effectiveness against influenza strains newly introduced in the human population [4]. Frontiers in Immunology | www.frontiersin.org van der Lubbe et al. Comparison Mini-HA to Full-Lenght HA

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