A group from Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA has shown that Lipid nanoparticle (LNP) enhances the efficacy of vaccines as a versatile adjuvant using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566475/
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. LNP-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized.
To demonstrate that this LNP formulation can provide adjuvant activity for other antigens, empty LNP (eLNP)- and AddaVax-adjuvanted SARS-CoV-2 spike protein subunit vaccines were evaluated using mice. Mice were immunized with a single dose of recombinant SARS-CoV-2 spike protein receptor binding domain (rRBD) adjuvanted with eLNP or AddaVax. As a positive control, another group of mice was immunized with nucleoside-modified RBD mRNA-LNP. It was found that LNP-adjuvanted vaccines elicited durable RBD-specific IgG titers that were significantly higher than the AddaVax-elicited responses.
To evaluate the adjuvant properties of LNPs with and without the ionizable lipid, mice were immunized with hemagglutinin recombinant protein (rHA) mixed with the two different formats of eLNP. The eLNP with the ionizable lipid showed high hemagglutinin inhibition titers, however, strikingly, eLNP not containing the ionizable lipid did not possess adjuvant activity.
IL-6 has been shown to be an early regulator of T follicular helper (Tfh) cell differentiation. Tfh cells are a subset of CD4+ T cells specialized in regulating affinity maturation of B cells in germinal centers (GCs). Induction of Tfh cells is critical for durable, protective Ab responses. It was found that the eLNP containing the ionizable lipid (eLNP) and mRNA-LNP induced large amounts of proinflammatory cytokines and chemokines, whereas the LNP lacking the ionizable lipid and AddaVax elicited lower cytokine and chemokine concentrations.
where, empty LNP (eLNP), AddaVax (an MF59-like adjuvant).