Recombinant M2e outer membrane vesicle vaccines protect against lethal influenza A challenge in BALB/c mice. Issue 10 (4th March 2016)

• Record Type: Journal Article
• Authors: Rappazzo, C. Garrett; Watkins, Hannah C.; Guarino, Cassandra M.; Chau, Annie; Lopez, Jody L.; DeLisa, Matthew P.; Leifer, Cynthia A.; Whittaker, Gary R.; Putnam, David
• Is Part Of: Vaccine. Volume 34:Issue 10(2016)
• Page Start: 1252
• Page End: 1258
• Publication Date: 2016-03-04
• Subjects: Outer membrane vesicles -- M2e subunit vaccines -- Universal influenza vaccine -- TLR agonists; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.01.028
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Engineered probiotic E. coli Nissle 1917 express and present influenza M2e peptides in outer membrane vesicles (M2e-OMVs). M2e-OMVs trigger the innate immune response predominantly through TLR2, TLR4, and TLR5 agonist activity. BALB/c mice vaccinated with M2e-OMVs are 100% protected against a lethal dose of H1N1 influenza A virus. Abstract: Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature.