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A Universal T Cell Vaccine Against Influenza A
Author(s) -
Tai Wendy ManTing,
Gilbert Brian Edward,
Corry David Brian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.853.11
Subject(s) - vaccination , medicine , tripeptide , immunology , cd8 , virology , virus , biology , immune system , peptide , biochemistry
A bivalent influenza virus (INFV) A vaccine composed of purified HA and NA has been available for INFV protection. However, this vaccine requires annual re‐administration. We have developed a novel T cell‐based vaccine that obviates this need. Our trivalent vaccine, is comprised of highly conserved peptides derived from H1N1 M2, HA, and NP peptides formulated with the TLR ligands (TLRLs), MPL, TDM and Poly (I:C) in a liposomal matrix. The tripeptide vaccine (50 μl) was given IN to WT mice on d‐21, ‐14, and ‐7 prior to challenge. Additional groups of WT and Rag1 −/− mice received only TLRL once ‐2d prior to challenge. All animals were challenged on d0 with LD 90 INFV A H3N2. Survival, weight loss, and symptom scores were monitored. On d0, tissues were collected and assessed for secretion of peptide specific IFN‐γ. In addition, lung cells were assessed for NP tetramer + CD8 cells and also lung histopathology. M2/TLRL and NP/TLRL immunizations provoked marked inflammation of the lung airways. Immunization with the tripeptide vaccine resulted in 100% survival and minimal weight loss and elevation of symptom scores relative to naïve controls (0% survival). M2 and NP specific IFN‐γ responses were observed predominantly in the lungs. Staining of lung cells with NP tetramer demonstrated ≈5% positive T cells. IN vaccination with TLRL ‐2d prior to challenge also protected WT and Rag1 −/− mice against lethal challenge.