Targeting of HA to chemokine receptors induces strong and cross-reactive T cell responses after DNA vaccination in pigs

•Rapid production is a key to effective influenza vaccines.•DNA vaccine efficacy was increased by targeting antigens to chemokine receptors.•Such targeting was particularly efficient at induction of broadly reactive T cells.•These T cells could mediate broad protection across different influenza sub...

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Bibliographic Details
Published in:Vaccine 2020-02, Vol.38 (6), p.1280-1285
Main Authors: Grodeland, Gunnveig, Fossum, Even, Bogen, Bjarne
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies, Viral - immunology
Antigen-presenting cells
Antigen-Presenting Cells - immunology
Antigens
APC-targeting
Avian flu
Cell adhesion & migration
Chemokine receptor
Chemokine receptors
Chemokines
Cross Protection
Deoxyribonucleic acid
DNA
DNA vaccine
DNA vaccines
Enzymes
Experiments
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinins
Hogs
Human populations
Immunoglobulin G
Immunoglobulins
Influenza
Influenza Vaccines - immunology
Laboratories
Livestock
Lymphocytes
Lymphocytes T
Orthomyxoviridae Infections - prevention & control
Orthomyxoviridae Infections - veterinary
Pandemics
Phosphatase
Pig
Plasmids
Proteins
Receptors
Receptors, Chemokine - immunology
Swine
T-Lymphocytes - immunology
Vaccination
Vaccines
Vaccines, DNA - immunology
Viruses
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Summary:•Rapid production is a key to effective influenza vaccines.•DNA vaccine efficacy was increased by targeting antigens to chemokine receptors.•Such targeting was particularly efficient at induction of broadly reactive T cells.•These T cells could mediate broad protection across different influenza subtypes. Efficient influenza vaccination of pigs can reduce disease burdens for the swine industry, but also represents an important measure for reducing the risk from novel viral reassortments that pose pandemic threats to the human population. Here, we have vaccinated pigs with a DNA vaccine encoding influenza virus hemagglutinin (HA) linked to the chemokine MIP1α that bind chemokine receptors 1, 3, and 5 expressed on antigen presenting cells (APC). Such MIP1α targeting of HA to APC enhanced induction of HA reactive antibodies, particularly IgG2. In addition, the MIP1α- HA vaccine induced strong T cell responses that could cross-react with different influenza subtypes. Thus, the strategy of targeting HA to chemokine receptors could be important for inducing broad protection against antigenically diverse influenza strains in pigs.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2019.11.084