Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus

Scientific Reports
Ida E M UddbackJan P Christensen

Abstract

The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months without showing any evidence of fading. Interestingly, the superior ability of the latter group to resist reinfection correlated with a higher number of antigen-specific CD8 T cells in the spleen. Thus, detailed analysis of the underlying CD8 T cell responses highlights the importance of T cells already positioned in the lungs prior to chal...Continue Reading

References

Aug 1, 1987·European Journal of Immunology·S QinH Waldmann
Jul 7, 1983·The New England Journal of Medicine·A J McMichaelP A Beare
Jan 1, 1994·Methods in Cell Biology·T C BeckerC B Newgard
Apr 1, 1996·Immunological Reviews·T M KündigR M Zinkernagel
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·R J HoganD L Woodland
Jun 29, 2005·The Journal of Experimental Medicine·Alan D RobertsDavid L Woodland
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sun-Sang J SungSteven R Beaty
Mar 24, 2006·Nature·Kyoko ShinyaYoshihiro Kawaoka
Mar 25, 2006·Science·Debby van RielThijs Kuiken
Jul 11, 2006·Immunological Reviews·Hirokazu HikonoDavid L Woodland
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy J PowellRichard W Dutton
Jun 29, 2007·Respiratory Research·Innocent N MbawuikeRobert B Couch
Sep 24, 2008·Vaccine·Brice BarefootElizabeth Ramsburg
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andres G GrandeaMatthew Moyle
Jan 18, 2011·Virology·Jeremy S Rossman, Robert A Lamb
Nov 24, 2011·PloS One·Elma Z TchilianPeter C L Beverley
Jan 6, 2012·Science Translational Medicine·Eleanor BarnesPaul Klenerman
Mar 24, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Patrick J LillieSarah C Gilbert
Oct 11, 2012·PloS One·Anne-Marie Carola AnderssonJan Pravsgaard Christensen
Dec 12, 2012·Frontiers in Immunology·Katherine KedzierskaVanessa Venturi
Mar 29, 2013·Journal of Virology·Maria Abildgaard SteffensenAllan Randrup Thomsen

❮ Previous
Next ❯

Citations

Oct 8, 2016·Scientific Reports·Ida E M UddbäckJan P Christensen
Feb 9, 2017·Clinical and Experimental Vaccine Research·Jung-Ok Kang, Jun Chang
Jan 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela Pizzolla, Linda M Wakim
Jun 11, 2020·Mucosal Immunology·Ida UddbäckJan P Christensen
Dec 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veronica MartiniElma Tchilian
Apr 27, 2021·Molecular Therapy. Methods & Clinical Development·Pin-Hung LinHung-Chih Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
lavage
FCS

Software Mentioned

TreeStar
FlowJo

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.