Abstract
Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose.
Highlights
Influenza A is a respiratory virus causing up to 5 million cases of severe illness and between 290,000 and 650,000 influenza-related deaths every year [1]
We investigated whether the immune response towards a HA-stem vaccine candidate that has previously shown to elicit bnAb responses in both mice and non-human primates [11], could be improved by presenting it on the surface of rigid capsid-like particles (CLP)
The majority of HAstem trimers were anchored to the CLP using multiple of the Spytags present at the C-terminus of each protomer
Summary
Influenza A is a respiratory virus causing up to 5 million cases of severe illness and between 290,000 and 650,000 influenza-related deaths every year [1]. Current influenza vaccines are directed against the major surface antigens, hemagglutinin (HA) and neuraminidase (NA) These vaccines generate strain-specific responses and need to be re-designed annually in response to antigenic shift and drift [2,3]. This cumbersome process is further complicated by the current production methods, which are largely still reliant on traditional egg-based propagation. This process is slow, costly and severely restricts the number of doses that can be produced for a given flu season, meaning we are left largely unprepared for pandemic outbreaks [4,5,6,7]. Several alternative approaches are being pursued with the aim to develop a universal flu vaccine (UFV), ideally offering life-long protection against a broad range of viral strains and subtypes including emerging pandemic strains [8,9]
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