Adjuvanticity of a CTLA-4 3′ UTR complementary oligonucleotide for emulsion formulated recombinant subunit and inactivated vaccines

Attenuation of interferon regulatory factor 7 activity in local infectious sites of trachea and lung for preventing the development of acute lung injury caused by influenza A virus

“…Also, the increased mRNA level of Irf7 in the lungs of the mice could be explained as a compensatory-augmentation-response induced by the reduced expression of IRF7 protein in the lungs. 49,50 The proposed connection of the IRF7-IFN-a pathway in the IAVinduced ALI could be supported by the other studies showing that the IFNAR-deficient mice infected with IAV were observed with decreased morbidity, lung damage, pro-inflammatory cytokines and lung-infiltrating inflammatory cells; treatment with IFN-a increased the morbidity of the influenza-infected mice, 34 antibody treatment delayed clinical signs, symptoms and lung pathology in IAV-infected swine, 51 and that CXCL10 was induced by IFN-a and antagonizing CXCL10-reduced symptom severity and delay mortality in IAV-infected ferrets. 52 Overall, the data presented here may deepen our understandings of the roles of locally produced IRF7 in defending IAV in the respiratory tract, as well as in causing ALI, if excessively activated.…”

“…5 Among the numerous members of type I IFNs, IFN-a and IFN-b are critically important in controlling the host innate immune response to IAV infection. 6 During the infection, IAV primarily targets the Abbreviations: ALI, acute lung injury; BALF, bronchoalveolar lavage fluid; CXCL10, C-X-C motif chemokine ligand 10; FBS, fetal bovine serum; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IAV, influenza A virus; IFN, interferon; IFNAR, interferon a and b receptor; IKKe, IjB kinase e; IRF7, interferon regulatory factor 7; ISGs, interferon-stimulated genes; LD 50 epithelial cells of the respiratory tract, and also infects local resident macrophages and dendritic cells. 1,7 To respond, these infected cells all produce type I IFNs; resident macrophages are the predominant producers.…”

“…), respectively. On day 5 p.i., the viral load of the lung tissues collected from the mice was analysed by cytopatic effect assay (a) for TCID50 and haemagglutination assay (b) for HA unit. Each symbol represents the viral load in the lungs from one mouse, and the horizontal line represents the mean value AE SD for each group (n = 6).…”

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

“…Several ASOs have been evaluated as adjuvants to enhance the immune response in experimental vaccines. These ASOs were designed against suppressor components such as cytokines [151,152], checkpoints [153,154], or transcription factors [148] (Figure 4). Using a neonatal mouse model of respiratory syncytial virus (RSV) infection, Ripple et al evaluated if local inhibition of IL-4Rα expression using an ASO specific for IL-4Rα during primary RSV infection would prevent Th2-biased responses to secondary RSV infection and improve longterm pulmonary function.…”

“…These vaccines were prepared with either recombinant PCV2b capsid protein or inactivated foot-and-mouth disease virus (FMDV) in ICR and BALB/c mice. The sequences of these anti-CTLA-4 ASOs, named CMD-1 and CMD-2, were complementary to conserved regions that are identical between human and mouse CTLA-4 mRNA present in 3' untranslated region (3' UTR) [153]. The authors found that CMD-1 inhibited the antigen-induced CTLA-4 up-regulation on the CD4+ T cells and enhanced the antibody response against both recombinant PCV2b capsid protein and inactivated FMDV in both ICR and BALB/c mice compared with the control group without ASOs (p < 0.05).…”