Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

PLoS Pathogens
Katie TungattAndrew K Sewell

Abstract

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the i...Continue Reading

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Citations

Dec 18, 2019·Annual Review of Animal Biosciences·Sabine E HammerJoan K Lunney
Jul 17, 2018·Frontiers in Immunology·Garry DoltonAndrew K Sewell
Feb 26, 2019·Frontiers in Immunology·Barbara HolzerElma Tchilian
Oct 13, 2020·Frontiers in Immunology·Massimiliano BaratelliMaria Montoya
Dec 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veronica MartiniElma Tchilian
Jun 19, 2021·Nature Reviews. Immunology·George M WarimweBryan Charleston
Nov 25, 2021·Science Translational Medicine·Joan K LunneyChaohui Dai

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Methods Mentioned

BETA
bronchoalveolar lavage
density gradient centrifugation
bronchoalveolar
lavage
ELISA
gel filtration
X-ray
ELISAs
flow cytometry

Software Mentioned

CCP4
DFEREGYSL
Motif Scan
Webtool
PyMOL Molecular Graphics System
PYMOL
COOT
FACSDiva
Unicorn
XDS

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