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Conference Paper: IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection
Title | IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection |
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Authors | |
Keywords | Cell-mediated immunity Universal vaccine |
Issue Date | 2014 |
Publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org |
Citation | Proceedings of the National Academy of Sciences, 2014, v. 111 n. 15, p. 5676-5681 How to Cite? |
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. |
Description | Session - Medical Sciences |
Persistent Identifier | http://hdl.handle.net/10722/196758 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID | |
Grants |
DC Field | Value | Language |
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dc.contributor.author | Doak, SA | - |
dc.contributor.author | Li, OTW | - |
dc.contributor.author | Mak, YW | - |
dc.contributor.author | Mok, KP | - |
dc.contributor.author | Nickolls, JM | - |
dc.contributor.author | Guan, Y | - |
dc.contributor.author | Waldmannc, TA | - |
dc.contributor.author | Peiris, JSM | - |
dc.contributor.author | Perera, LP | - |
dc.contributor.author | Poon, LLM | - |
dc.date.accessioned | 2014-04-28T08:38:59Z | - |
dc.date.available | 2014-04-28T08:38:59Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences, 2014, v. 111 n. 15, p. 5676-5681 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/196758 | - |
dc.description | Session - Medical Sciences | - |
dc.description.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. | - |
dc.language | eng | - |
dc.publisher | National Academy of Sciences. The Journal's web site is located at http://www.pnas.org | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences | - |
dc.subject | Cell-mediated immunity | - |
dc.subject | Universal vaccine | - |
dc.title | IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Doak, SA: sophiev@hku.hk | - |
dc.identifier.email | Li, OTW: litwo@hku.hk | - |
dc.identifier.email | Mak, YW: makyw@hkucc.hku.hk | - |
dc.identifier.email | Mok, KP: ch02mkp@hkucc.hku.hk | - |
dc.identifier.email | Guan, Y: yguan@hkucc.hku.hk | - |
dc.identifier.email | Peiris, JSM: malik@hkucc.hku.hk | - |
dc.identifier.email | Poon, LLM: llmpoon@hkucc.hku.hk | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1403684111 | - |
dc.identifier.pmid | 24706798 | - |
dc.identifier.pmcid | PMC3992686 | - |
dc.identifier.scopus | eid_2-s2.0-84898769488 | - |
dc.identifier.hkuros | 228685 | - |
dc.identifier.hkuros | 234948 | - |
dc.identifier.volume | 111 | - |
dc.identifier.issue | 15 | - |
dc.identifier.spage | 5676 | - |
dc.identifier.epage | 5681 | - |
dc.identifier.isi | WOS:000334288600058 | - |
dc.publisher.place | United States | - |
dc.relation.project | Control of Pandemic and Inter-pandemic Influenza | - |
dc.identifier.issnl | 0027-8424 | - |