T cell immune response to liposomal influenza A tri-peptide vaccine (130.2)

Abstract

Abstract A bivalent influenza virus (INFV) A vaccine composed of purified HA and NA surface proteins have long been available. Disadvantages of this vaccine include annual reformulation. We have developed a novel T cell-based vaccine comprised of short and highly conserved peptides derived from M2, HA, and NP peptides formulated with TLR ligands in a lipid matrix. We hypothesized that IN immunization with short and well conserved peptides will confer protection to lethally infected mice. The tri-peptide (TP) vaccine was given IN to mice on d-21, -14, and -7 prior to INFV A and B aerosol infection (d0). Control animals received only sham liposomes (DLPC). For memory studies, mice were infected on 60d or 90d post treatment. 100% survival was observed in TP treated vs. DLPC treated mice (<10%). PAS staining of lung sections showed reduced inflammation associated with TP treatment. Although TP treatments were not long lasting, it conferred partial protection to boosted mice (40% survival), and 17% NP+ CD8 T lungs cells were observed after booster. Lung viral burden was reduced by 2 log TP treated vs. naïve mice (d2). Divergent trends of IFN-γ and IL-6 production between TP treated and naïve animals on d6 and d8 post infection were observed. Our findings indicate that T cells play an important role in viral clearance and mediation of flu. Future studies will aim at the understanding of the recruitment and egress of these T cell populations.