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- Publisher Website: 10.1371/journal.pone.0033161
- Scopus: eid_2-s2.0-84858633511
- PMID: 22470440
- WOS: WOS:000303857100018
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Article: Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses
Title | Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses |
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Authors | |
Issue Date | 2012 |
Citation | PLoS ONE, 2012, v. 7, n. 3 How to Cite? |
Abstract | The available evidence suggests that protective immunity to Leishmania is achieved by priming the CD4+ Th1 response. Therefore, we utilised a reverse genetics strategy to generate influenza A viruses to deliver an immunogenic Leishmania peptide. The single, immunodominant Leishmania-specific LACK158-173 CD4+ peptide was engineered into the neuraminidase stalk of H1N1 and H3N2 influenza A viruses. These recombinant viruses were used to vaccinate susceptible BALB/c mice to determine whether the resultant LACK158-173-specific CD4+ T cell responses protected against live L. major infection. We show that vaccination with influenza-LACK158-173 triggers LACK158-173-specific Th1-biased CD4+ T cell responses within an appropriate cytokine milieu (IFN-γ, IL-12), essential for the magnitude and quality of the Th1 response. A single intraperitoneal exposure (non-replicative route of immunisation) to recombinant influenza delivers immunogenic peptides, leading to a marked reduction (2-4 log) in parasite burden, albeit without reduction in lesion size. This correlated with increased numbers of IFN-γ-producing CD4+ T cells in vaccinated mice compared to controls. Importantly, the subsequent prime-boost approach with a serologically distinct strain of influenza (H1N1->H3N2) expressing LACK158-173 led to a marked reduction in both lesion size and parasite burdens in vaccination trials. This protection correlated with high levels of IFN-γ producing cells in the spleen, which were maintained for 6 weeks post-challenge indicating the longevity of this protective effector response. Thus, these experiments show that Leishmania-derived peptides delivered in the context of recombinant influenza viruses are immunogenic in vivo, and warrant investigation of similar vaccine strategies to generate parasite-specific immunity. © 2012 Kedzierska et al. |
Persistent Identifier | http://hdl.handle.net/10722/241232 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Kedzierska, Katherine | - |
dc.contributor.author | Curtis, Joan M. | - |
dc.contributor.author | Valkenburg, Sophie A. | - |
dc.contributor.author | Hatton, Lauren A. | - |
dc.contributor.author | Kiu, Hiu | - |
dc.contributor.author | Doherty, Peter C. | - |
dc.contributor.author | Kedzierski, Lukasz | - |
dc.date.accessioned | 2017-05-26T03:37:10Z | - |
dc.date.available | 2017-05-26T03:37:10Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | PLoS ONE, 2012, v. 7, n. 3 | - |
dc.identifier.uri | http://hdl.handle.net/10722/241232 | - |
dc.description.abstract | The available evidence suggests that protective immunity to Leishmania is achieved by priming the CD4+ Th1 response. Therefore, we utilised a reverse genetics strategy to generate influenza A viruses to deliver an immunogenic Leishmania peptide. The single, immunodominant Leishmania-specific LACK158-173 CD4+ peptide was engineered into the neuraminidase stalk of H1N1 and H3N2 influenza A viruses. These recombinant viruses were used to vaccinate susceptible BALB/c mice to determine whether the resultant LACK158-173-specific CD4+ T cell responses protected against live L. major infection. We show that vaccination with influenza-LACK158-173 triggers LACK158-173-specific Th1-biased CD4+ T cell responses within an appropriate cytokine milieu (IFN-γ, IL-12), essential for the magnitude and quality of the Th1 response. A single intraperitoneal exposure (non-replicative route of immunisation) to recombinant influenza delivers immunogenic peptides, leading to a marked reduction (2-4 log) in parasite burden, albeit without reduction in lesion size. This correlated with increased numbers of IFN-γ-producing CD4+ T cells in vaccinated mice compared to controls. Importantly, the subsequent prime-boost approach with a serologically distinct strain of influenza (H1N1->H3N2) expressing LACK158-173 led to a marked reduction in both lesion size and parasite burdens in vaccination trials. This protection correlated with high levels of IFN-γ producing cells in the spleen, which were maintained for 6 weeks post-challenge indicating the longevity of this protective effector response. Thus, these experiments show that Leishmania-derived peptides delivered in the context of recombinant influenza viruses are immunogenic in vivo, and warrant investigation of similar vaccine strategies to generate parasite-specific immunity. © 2012 Kedzierska et al. | - |
dc.language | eng | - |
dc.relation.ispartof | PLoS ONE | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1371/journal.pone.0033161 | - |
dc.identifier.pmid | 22470440 | - |
dc.identifier.scopus | eid_2-s2.0-84858633511 | - |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | null | - |
dc.identifier.epage | null | - |
dc.identifier.eissn | 1932-6203 | - |
dc.identifier.isi | WOS:000303857100018 | - |
dc.identifier.issnl | 1932-6203 | - |