Abstract
Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.
Highlights
Activation of patternrecognition receptor (PRR) triggers cell signaling, which stimulates the production of proinflammatory cytokines, chemokines, and type I interferons (IFNs) that support the subsequent development of appropriate pathogen-specific adaptive immunity; PRR activation can be harnessed to accelerate and enhance the induction of vaccine- specific responses [1,2,3].To date, four major classes of PRRs have been described, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), C- type lectin receptors (CLRs) and retinoic acid-inducible gene-1 (RIG1)-like receptors [4]
Our previous study found that immunization with killed foot-and-mouth disease virus (FMDV) vaccine adjuvanted with CVC1302 induces the establishment of an immunocompetent microenvironment at the injection site, which promotes the recruitment of antigen-presenting cells (APCs), especially dendritic cells (DCs) [6]
The results indicate that significantly higher numbers of NP+ DCs (NP+, CD11c+, CD11b+ cells) were observed at the injection sites of mice immunized with NPCVC1302 as compared with those of mice immunized with NP alone, most notably at 3 dpi, which is consistent with the findings from our previous study
Summary
Activation of PRRs triggers cell signaling, which stimulates the production of proinflammatory cytokines, chemokines, and type I interferons (IFNs) that support the subsequent development of appropriate pathogen-specific adaptive immunity; PRR activation can be harnessed to accelerate and enhance the induction of vaccine- specific responses [1,2,3].To date, four major classes of PRRs have been described, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), C- type lectin receptors (CLRs) and retinoic acid-inducible gene-1 (RIG1)-like receptors [4]. CVC1302, which contains three types of PRR agonists, was demonstrated to boost the long-term humoral immunity induced by killed FMDV vaccine [5]. Owing to the lack of available fluorescently labeled FMDV- specific antibodies, we were unable to assess the ability of CVC1302 to promote the levels of antigen-positive APCs infiltrated in the injection sites and draining LNs in that previous study. As previous study showed that long-term humoral immunity induced by CVC1302-adjuvanted serotype O foot-and-mouth disease inactivated vaccine correlates with promoted TFH and germinal center responses in mice, and TFH were found to select high-affinity B cells during affinity maturation, so in this study, we utilized NP-OVA as a pattern antigen to analyze the high-affinity NP-specific antibody levels. Because MBCs do not actively secrete antibody in the absence of antigen-specific stimulation, CVC1302-induced LLPCs were hypothesized to be the cell type responsible for mediating long-term antibody production
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.
