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Vaccine. 2017 Sep 25;35(40):5373-5380. doi: 10.1016/j.vaccine.2017.08.013. Epub 2017 Aug 31.

A single dose and long lasting vaccine against pandemic influenza through the controlled release of a heterospecies tandem M2 sequence embedded within detoxified bacterial outer membrane vesicles.

Author information

1
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
2
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
3
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
4
Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
5
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
6
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA. Electronic address: dap43@cornell.edu.

Abstract

The influenza A virus undergoes genetic drift and shift, leaving the general population susceptible to emerging pandemic strains, despite seasonal flu vaccination. Here we describe a single dose influenza vaccine derived from recombinant outer membrane vesicles (rOMVs) that display an antigen-mapped heterospecies tandem sequence of the M2 protein from the influenza A virus, released over 30days from poly(lactic-co-glycolide) (PLGA) microparticles. Four weeks post vaccination, BALB/c mice developed high anti-M2e IgG titers that were equivalent to those generated at 8weeks in a typical prime/boost vaccine regimen. Challenge of mice with a lethal dose of mouse adapted influenza virus PR8 (H1N1) 10weeks post vaccination resulted in 100% survival for both rOMV single-dose microparticle and prime/boost vaccinated mice. Anti-M2e IgG1 and IgG2a antibody titers were weighted toward IgG1, but splenocytes isolated from rOMV single-dose microparticle vaccinated mice produced high levels of IFN╬│ relative to IL-4 in response to stimulation with M2e peptides, supporting a more Th1 biased immune response. The protective immune response was long lasting, eliciting sustained antibody titers and 100% survival of mice challenged with a lethal dose of PR8 six months post initial vaccination. Together, these data support the potential of controlled release rOMVs as an effective single dose, long lasting and rapidly effective vaccine to protect against influenza.

KEYWORDS:

Controlled release; Influenza; M2e; OMV; Outer membrane vesicle; Single dose

PMID:
28866291
DOI:
10.1016/j.vaccine.2017.08.013
[Indexed for MEDLINE]

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