Mini-hemagglutinin vaccination induces cross-reactive antibodies in pre-exposed NHP that protect mice against lethal influenza challenge

Joan E M Van Der Lubbe,Boerries Brandenburg,Johan W A Verspuij,Ramon Roozendaal,Liesbeth Dekking,Jeroen T B M Tolboom,Lisanne Tettero,Hanneke Schuitemaker,Harmjan Kuipers,Daniella Mortier,Willy M J M Bogers,Jeroen Huizingh,Roland C Zahn,Petra Mooij,Ted Kwaks,Gerrit Koopman,Wim Meijberg,Sonja P R Schmit-Tillemans

doi:10.1038/s41541-018-0063-7

Abstract

Seasonal vaccines are currently the most effective countermeasure against influenza. However, seasonal vaccines are only effective against strains closely related to the influenza strains contained in the vaccine. Recently a new hemagglutinin (HA) stem-based antigen, the so-called “mini-HA”, has been shown to induce a cross-protective immune response in influenza-naive mice and non-human primates (NHP). However, prior exposure to influenza can have a profound effect on the immune response to subsequent influenza infection and the protective efficacy of vaccination. Here we show that mini-HA, compared to a trivalent influenza vaccine (TIV), elicits a broadened influenza-specific humoral immune response in NHP previously exposed to influenza. Serum transfer experiments showed that antibodies induced by both mini-HA and seasonal vaccine protected mice against lethal challenge with a H1N1 influenza strain heterologous to the H1 HA included in the TIV. However, antibodies elicited by mini-HA showed an additional benefit of protecting mice against lethal heterosubtypic H5N1 influenza challenge, associated with H5 HA-specific functional antibodies.

Highlights

The most effective countermeasure available against influenza is vaccination
The cohort of nonhuman primates (NHP) (n = 11) used for the current study was previously exposed to influenza infection, which in some animals was preceded by a trivalent influenza vaccine (TIV) vaccination (n = 5), indicated by symbols in the figures
The antibody titers binding to the rHA H7 were significantly higher after immunization with mini-HA compared to the TIV (p < 0.01)

Summary

Introduction

The most effective countermeasure available against influenza is vaccination. Due to rapid accumulation of point mutations and reassortment the influenza virus evades the protective immune response elicited by prior infections or vaccination. As a consequence the strains included in the vaccine need yearly review. Influenza strains to be included in the vaccine are selected based on continuous surveillance of circulating strains.[1] Though the incidence and severity of annual influenza epidemics are greatly reduced by vaccines covering the circulating strains, influenza remains a major public health issue. Seasonal influenza vaccines are effective only against strains closely related to the vaccine strains, and do not protect against genetically drifted or influenza viruses newly introduced in the human population, resulting in a steep drop of vaccine effectiveness when vaccine strains are mismatched with circulating strains.[2,3] The 2009 swine flu pandemic and newly emerging influenza strains with pandemic potential, such as H5N1 and H7N9, underscore the need for more broadly protective influenza vaccines

Methods

Results

Conclusion