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.

Topical Adjuvant Application during Subcutaneous Vaccination Promotes Resident Memory T Cell Generation

“…In our models, protection from infection with OVA-expressing pathogens was observed even when the infection occurred in a separate compartment (i.e., i.v. or the respiratory tract) from the site of immunization (the skin and s.c. compartment) (15,16). To assess whether the skin compartment is protected by T RM generated via our immunization procedures, we employed a melanoma challenge model.…”

“…Using OVA protein as the model Ag and CpG ODN as the adjuvant, we previously showed that CpG ODN promotes the efficient generation of Ag-specific CD8 T cells in the circulation (13,14), and administering CpG ODN e.c. is superior to s.c. administration (14)(15)(16). We demonstrated the use of e.c.…”

“…Mice were e.c. immunized (primed and boosted) as previously described (16). In brief, dorsal hair were shaved, tape stripped (TS) with cellophane tape, and gently rubbed with acetone to increase skin permeability.…”

“…Furthermore, the memory T cells generated in this way are better able to provide long-term protection against i.v. Listeria infection or an intranasal challenge with influenza A virus (15,16), raising the prospect that e.c. CpG ODN adjuvant application could represent a promising approach to improve vaccine efficacy.…”

Construction and protective immunogenicity of DNA vaccine pNMB0315 against Neisseria�meningitidis serogroup B

“…In the present study, a recombinant pNMB0315 was constructed and transfected into eukaryotic cell lines, which effectively expressed rNMB0315 protein, indicating the successful construction of a DNA vaccine. CpG was used as an adjuvant to enhance immune effects of the DNA vaccine (19). CpGs are recognized by toll-like receptor 9 (TLR9), a receptor found on antigen presenting cells (APCs), which results in the activation of TLR9 and the enhancement of antigen presenting capacity of APCs (20,21).…”