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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | 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. |
| Description | Author Affiliation: Valkenburg SA ( Department of Pathology, Center of Influenza Research and School of Public Health, University of Hong Kong, Hong Kong.); |
| Abstract | 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, pandemic-2009 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD4-Positive T-Lymphocytes Immunology Influenza Vaccines Interleukin-15 Orthomyxoviridae Infections Prevention & Control Vaccinia Virus Adjuvants, Immunologic Administration & Dosage Animals Flow Cytometry Influenza A Virus, H1N1 Subtype Influenza A Virus, H3N2 Subtype Influenza A Virus, H7N7 Subtype Influenza A Virus, H7N9 Subtype Mice Mice, Inbred BALB C Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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