Human Serum Amyloid P Functions as a Negative Regulator of the Innate and Adaptive Immune Responses to DNA Vaccines

摘要: The utility of DNA vaccines has been limited by their failure to elicit sufficiently potent immune responses in many human applications, whereas vaccinations mice have very successful. However, the underlying mechanisms remain unknown. We hypothesize that serum amyloid P component (SAP), which a species-specific, DNA-binding ability, contributes differences between and then limits vaccine's efficacy vivo. In our study, vaccine-induced adaptive were also significantly decreased SAP (hSAP) transgenic mice. Using promonocytic cell line THP-1-derived macrophages as model, we found cells incubated with hSAP-DNA complex showed significant defects innate activations, mouse had similar, albeit weak, activities. hSAP inhibited functions two identified sentinels, high-mobility group B protein 1 antimicrobial peptide LL37, redirected update FcRs leading endocytosis endosomal degradation. chemical inhibitor strongly recovered suppressed presence enhanced immunogenicity Our data indicated is key negative regulator for may be partly responsible insufficient after humans. suppression novel strategy improving requires further clinical investigations.