Cargando…

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 respons...

Descripción completa

Detalles Bibliográficos
Autores principales: Qin, Zhen, Bouteau, Aurélie, Herbst, Christopher, Igyártó, Botond Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413714/
https://www.ncbi.nlm.nih.gov/pubmed/36032972
http://dx.doi.org/10.1101/2022.03.16.484616
_version_ 1784775817309454336
author Qin, Zhen
Bouteau, Aurélie
Herbst, Christopher
Igyártó, Botond Z.
author_facet Qin, Zhen
Bouteau, Aurélie
Herbst, Christopher
Igyártó, Botond Z.
author_sort Qin, Zhen
collection PubMed
description 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 responses, 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 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.
format Online
Article
Text
id pubmed-9413714
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-94137142022-08-27 Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion Qin, Zhen Bouteau, Aurélie Herbst, Christopher Igyártó, Botond Z. bioRxiv Article 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 responses, 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 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. Cold Spring Harbor Laboratory 2022-08-20 /pmc/articles/PMC9413714/ /pubmed/36032972 http://dx.doi.org/10.1101/2022.03.16.484616 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Qin, Zhen
Bouteau, Aurélie
Herbst, Christopher
Igyártó, Botond Z.
Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title_full Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title_fullStr Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title_full_unstemmed Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title_short Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
title_sort pre-exposure to mrna-lnp inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413714/
https://www.ncbi.nlm.nih.gov/pubmed/36032972
http://dx.doi.org/10.1101/2022.03.16.484616
work_keys_str_mv AT qinzhen preexposuretomrnalnpinhibitsadaptiveimmuneresponsesandaltersinnateimmunefitnessinaninheritablefashion
AT bouteauaurelie preexposuretomrnalnpinhibitsadaptiveimmuneresponsesandaltersinnateimmunefitnessinaninheritablefashion
AT herbstchristopher preexposuretomrnalnpinhibitsadaptiveimmuneresponsesandaltersinnateimmunefitnessinaninheritablefashion
AT igyartobotondz preexposuretomrnalnpinhibitsadaptiveimmuneresponsesandaltersinnateimmunefitnessinaninheritablefashion