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IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+T cells for heterosubtypic protection
by
Li, Olive T. W.
, Mok, Chris K. P.
, Mak, Polly W. Y.
, Valkenburg, Sophie A.
, Guan, Yi
, Waldmann, Thomas A.
, Poon, Leo L. M.
, Peiris, J. S. Malik
, Nicholls, John M.
, Perera, Liyanage P.
in
adjuvants
/ Adjuvants, Immunologic - administration & dosage
/ Animals
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - immunology
/ epitopes
/ Female
/ Flow Cytometry
/ H1N1 subtype influenza A virus
/ H3N2 subtype influenza A virus
/ H5N1 subtype influenza A virus
/ humans
/ Immunity
/ Immunization
/ Infections
/ Influenza
/ Influenza A virus
/ Influenza A Virus, H1N1 Subtype - immunology
/ Influenza A Virus, H3N2 Subtype - immunology
/ Influenza A Virus, H7N7 Subtype - immunology
/ Influenza A Virus, H7N9 Subtype - immunology
/ Influenza Vaccines - immunology
/ interleukin-15
/ Interleukin-15 - administration & dosage
/ Interleukin-15 - immunology
/ lungs
/ Medical Sciences
/ Mice
/ Mice, Inbred BALB C
/ neutralization
/ neutralizing antibodies
/ Orthomyxoviridae
/ Orthomyxoviridae Infections - immunology
/ Orthomyxoviridae Infections - prevention & control
/ Pandemics
/ Protein expression
/ Rodents
/ T cell receptors
/ T lymphocytes
/ Vaccination
/ Vaccines
/ Vaccinia virus
/ Vaccinia virus - immunology
/ viral load
/ viral proteins
/ Virology
/ Viruses
2014
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IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+T cells for heterosubtypic protection
by
Li, Olive T. W.
, Mok, Chris K. P.
, Mak, Polly W. Y.
, Valkenburg, Sophie A.
, Guan, Yi
, Waldmann, Thomas A.
, Poon, Leo L. M.
, Peiris, J. S. Malik
, Nicholls, John M.
, Perera, Liyanage P.
in
adjuvants
/ Adjuvants, Immunologic - administration & dosage
/ Animals
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - immunology
/ epitopes
/ Female
/ Flow Cytometry
/ H1N1 subtype influenza A virus
/ H3N2 subtype influenza A virus
/ H5N1 subtype influenza A virus
/ humans
/ Immunity
/ Immunization
/ Infections
/ Influenza
/ Influenza A virus
/ Influenza A Virus, H1N1 Subtype - immunology
/ Influenza A Virus, H3N2 Subtype - immunology
/ Influenza A Virus, H7N7 Subtype - immunology
/ Influenza A Virus, H7N9 Subtype - immunology
/ Influenza Vaccines - immunology
/ interleukin-15
/ Interleukin-15 - administration & dosage
/ Interleukin-15 - immunology
/ lungs
/ Medical Sciences
/ Mice
/ Mice, Inbred BALB C
/ neutralization
/ neutralizing antibodies
/ Orthomyxoviridae
/ Orthomyxoviridae Infections - immunology
/ Orthomyxoviridae Infections - prevention & control
/ Pandemics
/ Protein expression
/ Rodents
/ T cell receptors
/ T lymphocytes
/ Vaccination
/ Vaccines
/ Vaccinia virus
/ Vaccinia virus - immunology
/ viral load
/ viral proteins
/ Virology
/ Viruses
2014
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IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+T cells for heterosubtypic protection
by
Li, Olive T. W.
, Mok, Chris K. P.
, Mak, Polly W. Y.
, Valkenburg, Sophie A.
, Guan, Yi
, Waldmann, Thomas A.
, Poon, Leo L. M.
, Peiris, J. S. Malik
, Nicholls, John M.
, Perera, Liyanage P.
in
adjuvants
/ Adjuvants, Immunologic - administration & dosage
/ Animals
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD4-Positive T-Lymphocytes - immunology
/ epitopes
/ Female
/ Flow Cytometry
/ H1N1 subtype influenza A virus
/ H3N2 subtype influenza A virus
/ H5N1 subtype influenza A virus
/ humans
/ Immunity
/ Immunization
/ Infections
/ Influenza
/ Influenza A virus
/ Influenza A Virus, H1N1 Subtype - immunology
/ Influenza A Virus, H3N2 Subtype - immunology
/ Influenza A Virus, H7N7 Subtype - immunology
/ Influenza A Virus, H7N9 Subtype - immunology
/ Influenza Vaccines - immunology
/ interleukin-15
/ Interleukin-15 - administration & dosage
/ Interleukin-15 - immunology
/ lungs
/ Medical Sciences
/ Mice
/ Mice, Inbred BALB C
/ neutralization
/ neutralizing antibodies
/ Orthomyxoviridae
/ Orthomyxoviridae Infections - immunology
/ Orthomyxoviridae Infections - prevention & control
/ Pandemics
/ Protein expression
/ Rodents
/ T cell receptors
/ T lymphocytes
/ Vaccination
/ Vaccines
/ Vaccinia virus
/ Vaccinia virus - immunology
/ viral load
/ viral proteins
/ Virology
/ Viruses
2014
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IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+T cells for heterosubtypic protection
Journal Article
IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+T cells for heterosubtypic protection
2014
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Overview
Current influenza vaccines are ineffective against novel viruses and the source or the strain of the next outbreak of influenza is unpredictable; therefore, establishing universal immunity by vaccination to limit the impact of influenza remains a high priority. To meet this challenge, a novel vaccine has been developed using the immunogenic live vaccinia virus as a vaccine vector, expressing multiple H5N1 viral proteins (HA, NA, M1, M2, and NP) together with IL-15 as a molecular adjuvant. Previously, this vaccine demonstrated robust sterile cross-clade protection in mice against H5 influenza viruses, and herein its use has been extended to mediate heterosubtypic immunity toward viruses from both group 1 and 2 HA lineages. The vaccine protected mice against lethal challenge by increasing survival and significantly reducing lung viral loads against the most recent human H7N9, seasonal H3N2, pandemic2009 H1N1, and highly pathogenic H7N7 influenza A viruses. Influenza-specific antibodies elicited by the vaccine failed to neutralize heterologous viruses and were unable to confer protection by passive transfer. Importantly, heterologous influenza-specific CD4+ and CD8+ T-cell responses that were elicited by the vaccine were effectively recalled and amplified following viral challenge in the lungs and periphery. Selective depletion of T-cell subsets in the immunized mice revealed an important role for CD4+ T cells in heterosubtypic protection, despite low sequence conservation among known MHC-II restricted epitopes across different influenza viruses. This study illustrates the potential utility of our multivalent Wyeth/IL-15/5Flu as a universal influenza vaccine with a correlate of protective immunity that is independent of neutralizing antibodies.
Publisher
National Academy of Sciences
Subject
/ Adjuvants, Immunologic - administration & dosage
/ Animals
/ CD4-Positive T-Lymphocytes - immunology
/ epitopes
/ Female
/ H1N1 subtype influenza A virus
/ H3N2 subtype influenza A virus
/ H5N1 subtype influenza A virus
/ humans
/ Immunity
/ Influenza A Virus, H1N1 Subtype - immunology
/ Influenza A Virus, H3N2 Subtype - immunology
/ Influenza A Virus, H7N7 Subtype - immunology
/ Influenza A Virus, H7N9 Subtype - immunology
/ Influenza Vaccines - immunology
/ Interleukin-15 - administration & dosage
/ lungs
/ Mice
/ Orthomyxoviridae Infections - immunology
/ Orthomyxoviridae Infections - prevention & control
/ Rodents
/ Vaccines
/ Virology
/ Viruses
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