Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity

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.

Analysis of CVC1302-Mediated Enhancement of Monocyte Recruitment in Inducing Immune Responses

“…CVC1302 was prepared as the aqueous phase according to previous study [ 16 ]. OVA-ISA206, OVAF-ISA206, OVA-CVC1302-ISA206 and OVAF-CVC1302-ISA206 were prepared according to a previous study [ 17 ]. CVC1302 was mixed thoroughly with OVA or OVAF, then emulsified with ISA206.…”

The Mechanism of bnAb Production and Its Application in Mutable Virus Broad-Spectrum Vaccines: Inspiration from HIV-1 Broad Neutralization Research

“…After factors influencing the GC response were gradually uncovered, investigators began trying to exploit the GC reaction law to invest in vaccine development. To achieve long-lasting GC reactions, investigators mostly choose to achieve better activation of DC cells using traditional soluble protein antigens plus TLR agonists [ 129 , 130 , 131 ], or to achieve sustained presentation of antigens using a slow-release approach [ 132 ]. However, the broad spectrum of vaccines remains unsatisfactory, and understanding the role that mechanisms of bNAb generation actually play in vaccine applications may require intensive exploration and attempts to enable researchers to gain a greater understanding of immune mechanisms in vaccines to design truly well-established broad-spectrum vaccines against mutable viruses.…”

Increases in Cellular Immune Responses Due to Positive Effect of CVC1302-Induced Lysosomal Escape in Mice

“…Inguinal lymph nodes were collected from the immunized mice at 7 days postimmunization (dpi), and single lymphocytes were harvested as described previously [20]. Cells were stained for 30 min at 4 • C with the following mAbs: CD3-FITC, CD4-Percp-cy5.5 and CD8-APC.…”