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Conference Paper: IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection

TitleIL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection
Authors
Issue Date2014
PublisherNational 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?
AbstractCurrent 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.
DescriptionSession - Medical Sciences
Persistent Identifierhttp://hdl.handle.net/10722/196758
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDoak, SA-
dc.contributor.authorLi, OTW-
dc.contributor.authorMak, YW-
dc.contributor.authorMok, KP-
dc.contributor.authorNickolls, JM-
dc.contributor.authorGuan, Y-
dc.contributor.authorWaldmannc, TA-
dc.contributor.authorPeiris, JSM-
dc.contributor.authorPerera, LP-
dc.contributor.authorPoon, LLM-
dc.date.accessioned2014-04-28T08:38:59Z-
dc.date.available2014-04-28T08:38:59Z-
dc.date.issued2014-
dc.identifier.citationProceedings of the National Academy of Sciences, 2014, v. 111 n. 15, p. 5676-5681-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/196758-
dc.descriptionSession - Medical Sciences-
dc.description.abstractCurrent 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.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.titleIL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protectionen_US
dc.typeConference_Paperen_US
dc.identifier.emailDoak, SA: sophiev@hku.hk-
dc.identifier.emailLi, OTW: litwo@hku.hk-
dc.identifier.emailMak, YW: makyw@hkucc.hku.hk-
dc.identifier.emailMok, KP: ch02mkp@hkucc.hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1403684111-
dc.identifier.pmid24706798-
dc.identifier.pmcidPMC3992686-
dc.identifier.hkuros228685-
dc.identifier.hkuros234948-
dc.identifier.volume111-
dc.identifier.issue15-
dc.identifier.spage5676-
dc.identifier.epage5681-
dc.identifier.isiWOS:000334288600058-
dc.publisher.placeUnited States-

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