The BNT162b2 vaccine’s empty lipid nanoparticle is able to induce an NF-κB response

Abstract Lipid nanoparticles (LNP) are essential components of messenger RNA (mRNA) vaccines that have been a cornerstone the COVID-19 public health response. These LNPs used for cell entry and protection mRNA. Others shown LNP BNT162b2 vaccine is able to augment immune response against target. However, it unknown how this stimulates innate cells such as monocytes participate in engagement adaptive We THP-1 monocyte reporter line nuclear factor kappa B (NF-κB) interferon regulatory (IRF) activation understand if empty could stimulate comparison with toll-like receptor (TLR) agonists. With line, we show BNT162b2’s initiate NF-κB, but not IRF dose-dependent manner. The NF-κB was similar low doses R848, TLR 7/8 agonist, well LPS, TLR4 agonist. Next, evaluated NF-kB absence MyD88 or TRIF using knockout lines. demonstrate reduced both In comparison, LPS primarily stimulated through MyD88, R848 relies on pathways. Our data can key pathways suggesting master regulator may induced by current mRNA platform. Moreover, our suggest use signaling cascades induce activation. Understanding mechanisms behind immunostimulatory capacity shed light modulating these enhance design. Defense Health Program, HU00012120094