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.