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Article: Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses

TitleInduction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses
Authors
Issue Date2012
Citation
PLoS ONE, 2012, v. 7, n. 3 How to Cite?
AbstractThe 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 Identifierhttp://hdl.handle.net/10722/241232
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKedzierska, Katherine-
dc.contributor.authorCurtis, Joan M.-
dc.contributor.authorValkenburg, Sophie A.-
dc.contributor.authorHatton, Lauren A.-
dc.contributor.authorKiu, Hiu-
dc.contributor.authorDoherty, Peter C.-
dc.contributor.authorKedzierski, Lukasz-
dc.date.accessioned2017-05-26T03:37:10Z-
dc.date.available2017-05-26T03:37:10Z-
dc.date.issued2012-
dc.identifier.citationPLoS ONE, 2012, v. 7, n. 3-
dc.identifier.urihttp://hdl.handle.net/10722/241232-
dc.description.abstractThe 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.languageeng-
dc.relation.ispartofPLoS ONE-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleInduction of protective CD4+ T cell-mediated immunity by a Leishmania peptide delivered in recombinant influenza viruses-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0033161-
dc.identifier.pmid22470440-
dc.identifier.scopuseid_2-s2.0-84858633511-
dc.identifier.volume7-
dc.identifier.issue3-
dc.identifier.spagenull-
dc.identifier.epagenull-
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000303857100018-
dc.identifier.issnl1932-6203-

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