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O17.3 Il-4/il-13 inhibitor vaccines induce protective immunity by modulating innate lymphocytic, dendritic and macrophage cell subsets at the vaccination site
  1. Z Li,
  2. A Ng,
  3. S Trivedi,
  4. R Jackson,
  5. C Ranasinghe
  1. John Curtin School of Medical Research, TheAustralian National University

Abstract

Introduction We have created two novel poxviral vector-based HIV vaccines that transiently inhibit IL-4/IL-13 activity at the vaccination site (murine IL-13Rα2 or IL-4R antagonist) that induce high avidity HIV-specific CD8 T cells with better protective efficacy. Compared to the IL-13Rα2 adjuvanted vaccine, the IL-4R antagonist adjuvanted vaccine induced not only high avidity CD8 T cells but also excellent gag-specific IgG1 and IgG2a antibody differentiation similar to what has been observed in HIV elite controllers. In this study, how IL-4/IL-13 differentially regulate T and B cell immunity following intranasal fowl poxvirus vector based vaccination were evaluated.

Methods BALB/c mice were immunised intranasally with recombinant fowl poxvirus co-expressing IL-13Ra2 or IL-4R antagonist adjuvanted together with HIV antigens and wt BALB/c and IL-4, IL-13 gene knockout (KO) mice with the unadjuvanted HIV vaccine. 24 h to 7 days post vaccination different innate lymphocytic cell (ILC) and antigen presenting cell subsets recruited to the vaccination site were evaluated using multi-colour flow cytometry.

Results BALB/c mice that received the IL-13Ra2 and IL-4R antagonist vaccines showed significantly reduced IL-13 expression by ILC2 at the lung mucosae compared to the BALB/c that received the unadjuvanted vaccine (p < 0.001). Interestingly, the IL-13Ra2 adjuvanted vaccinated group showed significantly elevated ILC1-like cells expressing IFN-g compared to the IL-4R antagonist vaccine (p < 0.0001) or BALB/c mice given the FPV-HIV unadjuvanted vaccination (p < 0.001). Furthermore, IL-4 and IL-13 milieu also influenced the dendritic and macrophage cell subsets (i.e. CD11b+ CD103- DC, plasmacytoid DC, alveolar macrophages) recruited to the lung mucosae 24 h post vaccination.

Conclusion Our findings suggest that i) the outcome of a vaccine is determined within the first 24 h of vaccination, ii) ILC1-like cells most likely play a role in B cell immunity and iii) ILC2 are the major source of IL-13 that dampens CD8 T cell avidity by altering DC/macrophage recruitment to the vaccination site.

Disclosure of interest statement Authors have no conflicts of Interests. Work was supported by NHMRC and ACH2 EOI grants.

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