Future considerations for the mRNA-lipid nanoparticle vaccine platform.

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccines against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in humans that remain unanswered. Here we consider the immunological features of LNP components and off-target effects of the mRNA, both of which could increase the risk of side effects. We suggest ways to mitigate these potential risks by harnessing dendritic cell (DC) biology.

Bioactive Lipids in COVID-19-Further Evidence.

Previously, I suggested that arachidonic acid (AA, 20:4 n-6) and similar bioactive lipids (BALs) inactivate SARS-CoV-2 and thus, may be of benefit in the prevention and treatment of COVID-19. This proposal is supported by the observation that (i) macrophages and T cells (including NK cells, cytotoxic killer cells and other immunocytes) release AA and other BALs especially in the lungs to inactivate various microbes; (ii) pro-inflammatory metabolites prostaglandin E2 (PGE2) and leukotrienes (LTs) and anti-inflammatory lipoxin A4 (LXA4) derived from AA (similarly, resolvins, protectins and maresins derived from eicosapentaenoic acid: EPA and docosahexaenoic acid: DHA) facilitate the generation of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages respectively; (iii) AA, PGE2, LXA4 and other BALs inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) synthesis; (iv) mesenchymal stem cells (MSCs) that are of benefit in COVID-19 elaborate LXA4 to bring about their beneficial actions and (v) subjects with insulin resistance, obesity, type 2 diabetes mellitus, hypertension, coronary heart disease and the elderly have significantly low plasma concentrations of AA and LXA4 that may render them more susceptible to SARS-CoV-2 infection and cytokine storm that is associated with increased mortality seen in COVID-19. Statins, colchicine, and corticosteroids that appear to be of benefit in COVID-19 can influence BALs metabolism. AA, and other BALs influence cell membrane fluidity and thus, regulate ACE-2 (angiotensin converting enzyme-2) receptors (the ligand through which SARS-CoV2 enters the cell) receptors. These observations lend support to the contention that administration of BALs especially, AA could be of significant benefit in prevention and management of COVI-19 and other enveloped viruses.