Lack of evidence for intergenerational inheritance of immune resistance to infections

Kaufmann, Eva; Landekic, Marija; Downey, Jeffrey; Chronopoulos, Julia; Nezhad, Sara Teimouri; Tran, Kim A; Vinh, Donald C.; Barreiro, Luis B.; Divangahi, Maziar

doi:10.1038/s41590-021-01102-0

Cited by 22 publications

(19 citation statements)

References 16 publications

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“…A very interesting observation was that the improved heterologous protection induced by mRNA-LNPs on influenza infection was successfully passed down to the offspring. A number of recent studies reported evidence for transmission of either trained immunity or tolerance across generations in mice [ 23 , 64 ], although not all of them [ 65 ]. Our independent study initiated and performed before these data became public seem to support the existence of transgenerational inheritance of immune traits.…”

Section: Discussionmentioning

confidence: 99%

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

et al. 2022

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“…A very interesting observation was that the improved heterologous protection induced by mRNA-LNPs on influenza infection was successfully passed down to the offspring. A number of recent studies reported evidence for transmission of either trained immunity or tolerance across generations in mice (Bomans et al, 2018; Katzmarski et al, 2021), although not all of them (Kaufmann et al, 2022). Our independent study initiated and performed before these data become public seem to support the existence of transgenerational inheritance of immune traits.…”

Section: Discussionmentioning

confidence: 99%

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Qin

Igyártó

2022

Preprint

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Billions 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. Here we bring experimental evidence that pre-exposure to mRNA-LNPs or its LNP component has effects on both innate and adaptive immune responses. Pre-exposure to mRNA-LNPs led to long-term, platform-specific inhibition of the adaptive immune responses. As such, mice responded with lower antibody responses when exposed the second time to the mRNA-LNP platform, but with undisturbed adaptive immune responses to protein-based Alum or AddaVax-adjuvanted vaccines. On the other hand, we report that after pre-exposure to mRNA-LNPs, resistance of mice to heterologous infections with influenza virus and Candida albicans is likely enhanced. Interestingly, mice pre-exposed to mRNA-LNPs can pass down the acquired immune traits to their offspring, providing better protection. In summary, the mRNA-LNP vaccine platform induces long-term immunological changes that can affect both humoral responses and heterologous protection against infections. More studies are needed to understand in-depth the mechanisms responsible for these effects.

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“…Darwinian evolution through genetic variability and selection is a slow process, which cannot provide protection in the short term during a severe epidemic, while intergenerational transmission of resistance based on epigenetic processes has the potential to induce rapid protection in the next generation. Second, intergenerational transmission of traits induced by metabolic stresses or toxins in vertebrates has been demonstrated extensively, as also acknowledged by Kaufmann et al 1 . However, these are not adaptive processes, and it is highly unlikely that the epigenetic mechanisms transmitting these traits have persisted during evolution to induce deleterious effects in the progeny.…”

mentioning

confidence: 87%

“…We read with great interest the study by Kaufmann and colleagues investigating the possibility that protection to reinfection may be transmitted intergenerationally in mice 1 . The authors found no such inheritance of resistance in models using BCG, β-glucan or a Candida albicans infection as potential inducers of trained immunity.…”

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confidence: 99%

Reply to: ‘Lack of evidence for intergenerational inheritance of immune resistance to infections’

et al. 2022

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Lack of evidence for intergenerational inheritance of immune resistance to infections

Cited by 22 publications

References 16 publications

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Reply to: ‘Lack of evidence for intergenerational inheritance of immune resistance to infections’

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