Recombinant Surface Immunogenic Protein from <i>S. agalactiae</i>and hemocyanin from <i>Fisurella latimarginata</i>promote cross-presentation dependence on the TLR-4 signaling

Abstract Improved vaccine adjuvants are needed to address infectious diseases, cancer, and future pandemics. Toll-like receptors (TLRs) have been researched as targets of because they modulate the innate immune system activate adaptive immunity. TLR-based induce cross-presentation exogenous antigens CD8 T lymphocytes. TLR4 signaling recruits adapters myeloid differentiation marker 88 (MyD88), which mediates recycling endoplasmic reticulum fusion phagosome well TIR-domain-containing adapter-inducing interferon-β (TRIF), is essential for translocation from endosome cytosol. Given role agonists, most studies used ligands based on lipopolysaccharides, but these side effects (especially fever). Here we propose using protein-based agonists (TLR-4-PBA), multiple advantages adjuvants: They naturally biocompatible biodegradable substances that minimal reactogenicity toxicity. We studied mollusk hemocyanin Fissurella latimarginata(FLH) recombinant surface immunogenic protein Streptococcus agalactiae(rSIP). These two proteins differ significantly in their structure, show Th1 immunomodulatory properties. Using mouse bone marrow-derived dendritic cells pulsed with ovoalbumin (OVA), then showed rSIP FLH promote OT-I CD8+ This effect depends recruitment MyD88 TRIF. Studies progress evaluate IRF3 NF-κ B activation.Our results illustrate how TLR-4-PBAs could act a clinically useful adjuvant immunity response. FONDECYT 1201600 (MIB); FONDEF ID21I10370 (AEV), Instituto de Salud Pública Chile Funding (AEV, DD-D); ANID/PhD Nacional program 21210946 (MLS) 21200880 (DD-D); FONDAP 15130011 (MT, SL).