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. Issue 40 (25th September 2017)

• Record Type: Journal Article
• Authors: Watkins, Hannah C.; Pagan, Catalina L.; Childs, Hannah R.; Posada, Sara; Chau, Annie; Rios, Jose; Guarino, Cassandra; DeLisa, Matthew P.; Whittaker, Gary R.; Putnam, David
• Is Part Of: Vaccine. Volume 35:Issue 40(2017)
• Page Start: 5373
• Page End: 5380
• Publication Date: 2017-09-25
• Subjects: Outer membrane vesicle -- OMV -- M2e -- Controlled release -- Single dose -- Influenza; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.08.013
• Languages: English
• ISSNs: 0264-410X

Abstract

Graphical abstract: Highlights: OMVs carrying a heterospecies M2e sequence induces immune protection against influenza challenge. Immune protection is long lasting (beyond six months) with a single dose formulation. The single dose OMV-based formulation induces rapid onset of protective antibody titers. 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 30 days 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 8 weeks in a typical prime/boost vaccine regimen. Challenge of mice with a lethal dose of mouse adapted influenza virus PR8 (H1N1) 10 weeks 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 IFNγ 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.