For March 2021, we have selected: Krienke C. et al., A non-inflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 2021; 371: 145-153. doi: 10.1126/science.aay3638.
Treating autoimmune disease with immunomodulant agents without compromising the function of the immune system is a challenge, which has become particularly important in the pandemic condition where immunosuppression might be fatal for patients treated with ongoing therapies for autoimmune disorders, i.e., multiple sclerosis. As a consequence, many patients did not receive the treatment to reduce the risk of Covid-19 disease but with the risk of a severe development of the previous ongoing disease.
In this scenario, our COVID-19 paper of the month opens an innovative possibility to treat this group of neurological patients starting from the study of an experimental autoimmune encephalomyelitis.
Our authors of the months tested a vaccine of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1ψ mRNA) coding for disease-related autoantigens. This vaccine resulted in antigen presentation on splenic CD11c+ antigen presenting cells in the absence of costimulatory signals. In mouse models of multiple sclerosis, this vaccine showed efficacy in disease suppression due to the increment of regulatory T cells and reduction of effector T cells.
The authors hypothesized that the use of such m1ψ mRNA for in vivo delivery of autoimmune disease target antigens into CD11c+ antigen presenting cells (APCs) in a noninflammatory context would enable systemic tolerogenic antigen presentation in lymphoid tissues. Krienke et al. demonstrated with several experiments and at single-cell resolution that this vaccine was able to trigger the generation of different antigen-specific CD4+ T cell subpopulations with distinct functional states. Importantly, the experiments listed in our paper of the month showed that the selective delivery of autoantigens into CD11c+ APCs resident in lymphoid tissues exploited a highly effective natural mechanism for induction and maintenance of peripheral tolerance. Importantly, the T regulatory cells stimulated by this vaccine executed strong bystander immunosuppression and thus improve the experimental autoimmune disease induced by cognate and noncognate autoantigens.
Our paper of the month gives hope to us that the scenario of potential control of even complex autoimmune diseases without compromising the normal action of the immune system. Further studies on patients are necessary to develop this type of vaccine for clinical practice.