Good news! Sometimes it is not just the vaccine itself that makes the vaccine powerful!
""In principle, this compound can be added to any vaccine to enhance its action," ... "Adjuvants are like rocket fuel for the immune system. PVP-037 is one of the most active adjuvants we've discovered, and we think it induces a greater, more durable, and broader immune response to vaccines." ...
PVP-037 belongs to a family of molecules called imidazopyrimidines, which the study found to be active immunomodulators. PVP-037 and its analogs target the innate immune system, stimulating the pattern-recognition receptors TLR7 and TLR8 on antigen-presenting cells such as monocytes and dendritic cells. ..."
From the abstract:
"Vaccination can help prevent infection and can also be used to treat cancer, allergy, and potentially even drug overdose. Adjuvants enhance vaccine responses, but currently, the path to their advancement and development is incremental. We used a phenotypic small-molecule screen using THP-1 cells to identify nuclear factor-κB (NF-κB)–activating molecules followed by counterscreening lead target libraries with a quantitative tumor necrosis factor immunoassay using primary human peripheral blood mononuclear cells. Screening on primary cells identified an imidazopyrimidine, dubbed PVP-037. Moreover, while PVP-037 did not overtly activate THP-1 cells, it demonstrated broad innate immune activation, including NF-κB and cytokine induction from primary human leukocytes in vitro as well as enhancement of influenza and SARS-CoV-2 antigen-specific humoral responses in mice. Several de novo synthesis structural enhancements iteratively improved PVP-037’s in vitro efficacy, potency, species-specific activity, and in vivo adjuvanticity. Overall, we identified imidazopyrimidine Toll-like receptor-7/8 adjuvants that act in synergy with oil-in-water emulsion to enhance immune responses."
From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation (open access)
Fig. 2. Iterative PVP-037–based SAR identified highly potent analogs in vitro that were effective adjuvants in vivo.
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