Following injury/infection, epithelial cells release cytokines IL-25 and IL-33 which activate ILC2 cells to express IL-5, IL-9, IL-13, and potentially small amounts of IL-4 [69]. Following intranasal infection of mice with a recombinant influenza A virus, activated ILC2 accumulate in the lung and express not only IL-5, IL-9, PLX3397 IL-13 but also amphiregulin (Areg), the ligand for EGFR which drives epithelial cell proliferation and tissue repair [70]. In the context of an attenuated vaccine similar ILC2 activation and IL-13 expression will have a negative impact

upon the resulting quality and magnitude of the Th1 anti-viral response. Potential additional sources of IL-4 during innate responses may include stimulation of basophils [71] and activated iNKT2 cells [72]. Poxviruses devote a

large proportion of the genomic information to express factors that modulate and evade the host’s antiviral innate and adaptive immune responses [73]. Of particular relevance to this study are factors secreted from pox virus infected cells which modulate the balance of Th1 and Th2 immunity. VV is known to express Ibrutinib molecular weight soluble type-I and type-II IFN binding proteins which sequester IFN-α and IFN-γ, respectively [74] and [75] VV also expresses soluble high affinity decoy receptors for TNF-α, and IL-18 which bind and prevent these cytokines from interacting with the natural receptors [76] and [77]. Poxviruses apply significant resources into reducing the activity of these antiviral cytokines which are required for activation of type-1 ILC i.e. type-I IFNs and IL-18, or neutralise the major secreted antiviral products, i.e. IFN-γ, TNF-α. IL-18 is critical for strong antiviral Th1 immunity, indeed with IL-18−/− mice the immune response following poxvirus infection is screwed towards a Th2 Phosphoprotein phosphatase cytokine profile (enhanced IL-4 and IL-10), reduced cytotoxic NK and CD8+ T cell responses and enhanced populations of suppressive Treg cells

[78]. Recent studies have demonstrated that deletion of the MVA IL-18BP gene can significantly enhance the efficacy of MVA vectored vaccines with increases in the HIV specific CD8+ and CD4+ T cell populations following immunisation [79]. In conclusion, our data indicate that transiently neutralising of IL-13 activity specifically at the priming cell milieu can significantly improve the avidity of the resulting HIV specific CD8+ T cell responses. However, the transient co-neutralisation of both IL-4 and IL-13 activity at the vaccination site is greatly beneficial in the induction of both gag-specific IgG1 and IgG2a antibody immunity, unlike the IL-13Rα2 adjuvanted vaccine that only has the capacity to induce IgG1 antibodies while inhibiting IgG2a.