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.
Highlights
Influenza virus belongs to the Orthomyxoviridae family of enveloped negative-sense, single-stranded segmented RNA viruses
We found that epicutaneous CpG ODN drove both CD8 T cell and antibody responses against influenza A virus (IAV)
To assess the ability of epicutaneous CpG ODN (ecCpG) adjuvant to provide protection from intranasal IAV infection, naive C57BL/6 mice or mice immunized with the OVA antigen subcutaneously or scOVA with ecCpG adjuvant were challenged with PR8-OVA 5 or 30 days post-immunization
Summary
Influenza virus belongs to the Orthomyxoviridae family of enveloped negative-sense, single-stranded segmented RNA viruses. Of the three subtypes of influenza viruses, influenza A virus (IAV) can infect many different species, including humans, other mammals, and birds. IAV is a highly contagious human respiratory pathogen and the cause of all influenza pandemics with a large impact on global health. Annual vaccination against seasonal influenza epidemics is recommended by governmental health organizations [1].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
