Abstract
Despite the possibility of combining Toll-like receptor (TLR) ligands as adjuvants to improve vaccine efficacy, it remains unclear which combinations of TLR ligands are effective or what their underlying mechanisms may be. Here, we investigated the mechanism of action of L-pampo, a proprietary adjuvant composed of TLR1/2 and TLR3 ligands. L-pampo dramatically increased humoral immune responses against the tested target antigens, which was correlated with an increase in follicular helper T cells and the maintenance of antigen-specific CD4+ T cells. During the initial priming phase, in contrast to the induction of type I interferon (IFN) and pro-inflammatory cytokines stimulated by polyI:C, L-pampo showed a greatly diminished induction of type I IFN, but not of other cytokines, and remarkably attenuated IRF3 signaling, which appeared to be critical to L-pampo-mediated adjuvanticity. Collectively, our results demonstrate that the adjuvant L-pampo contributes to the promotion of antigen-specific antibodies and CD4+ T cell responses via a fine regulation of the TLR1/2 and TLR3 signaling pathways, which may be helpful in the design of improved vaccines.
Highlights
Toll-like receptor (TLR) ligands are widely studied as adjuvants, in combination with subunit vaccines, because they modulate immune responses, thereby establishing a sufficient amount of protective immunity[1,2]
We have previously reported that L-pampo, a proprietary adjuvant composed of Pam3Csk[4] (Pam3) and polyinosinic:polycytidylic acid, induced a much stronger humoral immune response to surface antigens of hepatitis B virus (HBV) than aluminum hydroxide[16]
We report an efficacious combination of TLR ligands that synergistically enhances the antibody responses against two different protein antigens
Summary
Toll-like receptor (TLR) ligands are widely studied as adjuvants, in combination with subunit vaccines, because they modulate immune responses, thereby establishing a sufficient amount of protective immunity[1,2]. Some combinations of TLR ligands synergistically enhance both the magnitude and quality of the immune response, including the generation of follicular helper T (Tfh) cells, the survival of antigen-presenting cells (APCs), and the affinity of antibodies[5,6]. When L-pampo is used as an adjuvant in a protein immunization system, it contributes to the maintenance of antigen-specific CD4+ T cell responses by regulating the IRF signaling pathway and type I IFN production. We propose that L-pampo adjuvanticity significantly modulates the innate cytokine environment and maintains antigen-specific CD4+ T cells during the memory phase, which leads to the expansion of functional CD4+ T cells, GC B cells and the enhanced production of class-switched antibodies, most likely amplified upon boosting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
