Pre-exposure to mRNA-LNP Inhibits Adaptive Immune Responses and Alters Innate Immune Fitness in an Inheritable Fashion
Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform's true impact on human health.
Qin, Zhen; Bouteau, Aurélie; Herbst, Christopher; and Igyártó, Botond Z., "Pre-exposure to mRNA-LNP Inhibits Adaptive Immune Responses and Alters Innate Immune Fitness in an Inheritable Fashion" (2022). Department of Microbiology and Immunology Faculty Papers. Paper 162.
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This article is the author's final published version in PLoS Pathogens, Volume 18, Issue 9, Sept. 2022, Article number e1010830.
The published version is available at https://doi.org/10.1371/journal.ppat.1010830.
Copyright © 2022 Qin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.