Immune potentiator for increased safety and improved protection of vaccines by NF-kB modulation

Abstract

Many modern vaccines include adjuvants that activate the immune system and provide an enhanced humoral or cellular response. Current approved adjuvants are unable to provide desired responses against some pathogens (e.g. HIV or dengue). Many new adjuvants 15

Small Molecule NF-kB Inhibitors as Immune Potentiators for Enhancement of Vaccine Adjuvants

“…2a-f). Consistent with our previous findings 5 , CpG induced TNF- and IL-6 expression peaked at 1 h. Interestingly, CpG combined with either capsaicin or honokiol had increased IFN-γ levels at 24 h compared to CpG alone (8 fold and 9 fold, respectively) and slightly elevated MCP-1 levels (2.5 and 2 fold, respectively), demonstrating that both capsaicin and honokiol are acting to potentiate the immune response and are not simply suppressing immune activation. We next wanted to understand how changing the dose would alter innate and adaptive immune responses.…”

“…Of the molecules we tested, honokiol and capsaicin proved to be effective at both limiting inflammation and potentiating the protective response. Through knockout studies, we demonstrate that the increase in antigen specific antibodies is independent from the anti-inflammatory activity, which is congruent with our previous studies 5 . To determine if these small molecules could be improved by chemical synthesis, we explored derivatives of honokiol and found several promising candidates for potential use in vaccines.…”

“…[15][16][17] We previously determined that CpG-induced TNF- and IL-6 peak at 1 h post-vaccination. 5 Mice vaccinated with CpG demonstrated high levels of TNF- (1067 pg/mL) (Fig. 1b).…”

“…[2][3][4] We recently reported that vaccines could be improved through the use of a peptide NF-B inhibitor, SN50 in combination with an immune adjuvant. 5 The addition of SN50 to adjuvanted vaccines led to increased safety of the adjuvant while enhancing protection against disease. Although this method proved both general across a wide range of adjuvants and effective against antigens of a variety of diseases, it still required a large amount of the peptide to enable optimal safety and protection.…”