tetano
Editor, Senior Moderator
Scand J Immunol
. 2021 Dec 19;e13128.
doi: 10.1111/sji.13128. Online ahead of print.
Intranasal delivery of a cDC1 targeted influenza vaccine with poly(I:C) enhances T cell responses and protects against influenza infection
Anna Lysén[SUP] 1 [/SUP], Arnar Gudjonsson[SUP] 1 [/SUP], Demo Yemane Tesfaye[SUP] 1 [/SUP], Sonja Bobic[SUP] 1 [/SUP], Malin Bern[SUP] 2 3 [/SUP], Bjarne Bogen[SUP] 1 2 [/SUP], Even Fossum[SUP] 1 [/SUP]
Affiliations
Abstract
Targeting antigens to dendritic cells represent a promising method for enhancing immune responses against specific antigens. However, many studies have focused on systemic delivery (intravenous or intraperitoneally) of targeted antigen, approaches that are not easily transferable to humans. Here we evaluate the efficacy of an influenza vaccine targeting Xcr1[SUP]+[/SUP] cDC1 administered by intranasal immunization. Intranasal delivery of antigen fused to the chemokine Xcl1, the ligand of Xcr1, resulted in specific uptake by lung CD103[SUP]+[/SUP] cDC1. Interestingly, intranasal immunization with influenza A/PR/8/34 hemagglutinin (HA) fused to Xcl1, formulated with poly(I:C), resulted in enhanced induction of antigen specific IFNγ[SUP]+[/SUP] CD4[SUP]+[/SUP] and IFNγ[SUP]+[/SUP] CD8[SUP]+[/SUP] T cell responses in lung compared non-targeted anti-NIP-HA (αNIP-HA). Induction of antibody responses was, however, similar in Xcl1-HA and αNIP-HA immunized mice, but significantly higher than in mice immunized with monomeric HA. Both Xcl1-HA and αNIP-HA vaccines induced full protection when mice were challenged with a lethal dose of influenza PR8 virus, reflecting the strong induction of HA specific antibodies. Our results demonstrate that i.n. delivery of Xcl1-HA is a promising vaccine strategy for enhancing T cell responses in addition to inducing of strong antibody responses.
Keywords: Dendritic cell; Influenza; Intranasal immunization; Xcl1; Xcr1.
. 2021 Dec 19;e13128.
doi: 10.1111/sji.13128. Online ahead of print.
Intranasal delivery of a cDC1 targeted influenza vaccine with poly(I:C) enhances T cell responses and protects against influenza infection
Anna Lysén[SUP] 1 [/SUP], Arnar Gudjonsson[SUP] 1 [/SUP], Demo Yemane Tesfaye[SUP] 1 [/SUP], Sonja Bobic[SUP] 1 [/SUP], Malin Bern[SUP] 2 3 [/SUP], Bjarne Bogen[SUP] 1 2 [/SUP], Even Fossum[SUP] 1 [/SUP]
Affiliations
- PMID: 34923667
- DOI: 10.1111/sji.13128
Abstract
Targeting antigens to dendritic cells represent a promising method for enhancing immune responses against specific antigens. However, many studies have focused on systemic delivery (intravenous or intraperitoneally) of targeted antigen, approaches that are not easily transferable to humans. Here we evaluate the efficacy of an influenza vaccine targeting Xcr1[SUP]+[/SUP] cDC1 administered by intranasal immunization. Intranasal delivery of antigen fused to the chemokine Xcl1, the ligand of Xcr1, resulted in specific uptake by lung CD103[SUP]+[/SUP] cDC1. Interestingly, intranasal immunization with influenza A/PR/8/34 hemagglutinin (HA) fused to Xcl1, formulated with poly(I:C), resulted in enhanced induction of antigen specific IFNγ[SUP]+[/SUP] CD4[SUP]+[/SUP] and IFNγ[SUP]+[/SUP] CD8[SUP]+[/SUP] T cell responses in lung compared non-targeted anti-NIP-HA (αNIP-HA). Induction of antibody responses was, however, similar in Xcl1-HA and αNIP-HA immunized mice, but significantly higher than in mice immunized with monomeric HA. Both Xcl1-HA and αNIP-HA vaccines induced full protection when mice were challenged with a lethal dose of influenza PR8 virus, reflecting the strong induction of HA specific antibodies. Our results demonstrate that i.n. delivery of Xcl1-HA is a promising vaccine strategy for enhancing T cell responses in addition to inducing of strong antibody responses.
Keywords: Dendritic cell; Influenza; Intranasal immunization; Xcl1; Xcr1.