Abstract
The extracellular domain of influenza M2 protein (M2e) is highly conserved and is a promising target for development of universal influenza vaccines. Here, we synthesized a peptide vaccine consisting of M2e epitope linked to a fibrillizing peptide, which could self-assemble into nanoparticle in physiological salt solutions. When administrated into mice without additional adjuvant, the influenza A M2e epitope-bearing nanoparticles induced antibodies against M2e of different influenza subtypes. Comparing with other M2e-based vaccine, these M2e nanoparticles did not induce immune response against the fibrillizing peptide, demonstrating minimal immunogenicity of vaccine carrier. Furthermore, vaccination with M2e-based nanoparticles did not only protect mice against homologous challenge of influenza PR8 H1N1 virus, but also provide protection against heterologous challenge of highly pathogenic avian influenza H7N9 virus. These results indicated that M2e-based self-assembled nanoparticle vaccine is safe and can elicit cross-protection, therefore is a promising candidate of universal influenza vaccines.
Highlights
Influenza remains as a great threat to public health despite that it has been studied for over 100 years since 1918
M2 protein (M2e) and Q11 specific antibodies were measured by Enzymelinked Immunosorbent Assay (ELISA)
We previously reported that a 23-mer M2e peptide could partially selfassemble into polymer through intra-peptide disulfide bonds and induce M2e-specific immune response with adjuvants in experimental mice (Wu et al, 2007; Zou et al, 2017)
Summary
Influenza remains as a great threat to public health despite that it has been studied for over 100 years since 1918. The seasonal flu epidemics cause about 3–5 million cases of severe illness and 290,000 to 650,000 deaths around the world annually (World Health Organization [WHO], 2018). Viruses could escape from the protection by rapid antigenic drift due to the accumulation of mutations on the antibody binding site of HA protein and make vaccine ineffective (Ilyushina et al, 2019). The antigenic components of influenza vaccine need to be updated every year to catch up with the change of epidemic viruses (Krammer and Palese, 2015). The viral antigen components in seasonal vaccines are selected based on the influenza surveillance data and epidemic prediction (Auladell et al, 2019). Seasonal flu vaccine efficacy is determined by the similarity between the vaccine strains and circulating viruses (Estrada and Schultz-Cherry, 2019). It has been suggested that the ineffectiveness of seasonal flu vaccine caused significant morbidity and mortality
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