Protective efficacy of a bacterially produced modular capsomere presenting M2e from influenza: Extending the potential of broadly cross-protecting epitopes

Wibowo, Nani, Hughes, Fiona K., Fairmaid, Emily J., Lua, Linda H. L., Brown, Lorena E. and Middelberg, Anton P. J. (2014) Protective efficacy of a bacterially produced modular capsomere presenting M2e from influenza: Extending the potential of broadly cross-protecting epitopes. Vaccine, 32 29: 3651-3655. doi:10.1016/j.vaccine.2014.04.062


Author Wibowo, Nani
Hughes, Fiona K.
Fairmaid, Emily J.
Lua, Linda H. L.
Brown, Lorena E.
Middelberg, Anton P. J.
Title Protective efficacy of a bacterially produced modular capsomere presenting M2e from influenza: Extending the potential of broadly cross-protecting epitopes
Journal name Vaccine   Check publisher's open access policy
ISSN 0264-410X
1873-2518
Publication date 2014-06-17
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.vaccine.2014.04.062
Open Access Status DOI
Volume 32
Issue 29
Start page 3651
End page 3655
Total pages 5
Place of publication London, United Kingdom
Publisher Elsevier Ltd
Language eng
Subject 2400 Immunology and Microbiology
2725 Infectious Diseases
2739 Public Health, Environmental and Occupational Health
3400 Veterinary
1313 Molecular Medicine
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 105 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.
Keyword Capsomere
E. coli
Rapid manufacture
Vaccine
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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