title: Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections.
abstract: Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with sc protein immunization to improve protection against influenza A virus (IAV) infections using a mouse model. We found enhanced long-term protection with epicutaneous CpG ODN (ecCpG) compared to subcutaneous CpG ODN (scCpG) as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with IAV infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against IAV infection.
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Wing Ki
authors.initials: WK
authors.lastname: Cheng
authors.affiliation: Department of Microbiology and Immunology, Faculty of Science, Life Sciences Institute, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Adam William
authors.initials: AW
authors.lastname: Plumb
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Jacqueline Cheuk-Yan
authors.initials: JC
authors.lastname: Lai
authors.affiliation: Department of Microbiology and Immunology, Faculty of Science, Life Sciences Institute, The University of British Columbia, Vancouver, BC, Canada; Department of Zoology, Faculty of Science, Life Sciences Institute, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ninan
authors.initials: N
authors.lastname: Abraham
authors.affiliation: Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: Dutz
keywords: CpG oligodeoxynucleotide; T cell memory; antibody production; influenza vaccines; skin vaccination