title: Protective efficacy of a bacterially produced modular capsomere presenting M2e from influenza: extending the potential of broadly cross-protecting epitopes.
abstract: Influenza A viruses drift and shift, emerging as antigenically distinct strains that lead to epidemics and pandemics of varying severity. Even epitopes associated with broad cross-protection against different strains, such as the ectodomain of matrix protein 2 (M2e), mutate unpredictably. Vaccine protective efficacy is only ensured when the emerging virus lies within the vaccine's cross-protective domain, which is poorly defined in most situations. When virus emerges outside this domain it is essential to rapidly re-engineer the vaccine and hence re-center the cross-protective domain on the new virus. This approach of vaccine re-engineering in response to virus change is the cornerstone of the current influenza control system, based on annual prediction and/or pandemic reaction. This system could become more responsive, and perhaps preventative, if its speed could be improved. Here, we demonstrate vaccine efficacy of a rapidly manufacturable modular capsomere presenting the broadly cross-protecting M2e epitope from influenza. M2e inserted into a viral capsomere at the DNA level was expressed in Escherichia coli as a fusion protein (Wibowo et al., 2013). Immunization of mice with this modular capsomere adjuvanted with conventional aluminum hydroxide induced high (more than 10(5) endpoint titer) levels of M2e-specific antibodies that reduced disease severity and viral load in the lungs of challenged mice. The combination of rapid manufacturability of modular capsomere presented in this study, and the established cross-protective efficacy of M2e, allow rapid matching of vaccine to the circulating virus and hence rapid re-centering of the vaccine's cross-protective domain onto the virus. This approach synergizes the discussed benefits of broadly cross-protecting epitopes with rapid scale-up vaccine manufacture using microbial cell factories.
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Centre for Biomolecular Engineering, St Lucia, QLD 4072, Australia.
authors.forename: Nani
authors.initials: N
authors.lastname: Wibowo
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Centre for Biomolecular Engineering, St Lucia, QLD 4072, Australia.
authors.forename: Fiona K
authors.initials: FK
authors.lastname: Hughes
authors.affiliation: The University of Melbourne, Department of Microbiology and Immunology, Parkville, VIC 3010, Australia.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Fairmaid
authors.affiliation: The University of Queensland, Protein Expression Facility, St Lucia, QLD 4072, Australia.
authors.forename: Linda H L
authors.initials: LH
authors.lastname: Lua
authors.affiliation: The University of Melbourne, Department of Microbiology and Immunology, Parkville, VIC 3010, Australia.
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Centre for Biomolecular Engineering, St Lucia, QLD 4072, Australia. Electronic address: a.middelberg@uq.edu.au.
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D017951:Antigen Presentation; D056738:Cross Protection; D000939:Epitopes / Q000276:immunology*; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Capsomere; E. coli; M2e; Rapid manufacture; Vaccine