"Introduction
The mRNA-LNP vaccine platform gained much attention with the ongoing SARS-CoV-2 pandemic. Initially, this vaccine platform was thought to be non-inflammatory since the mRNA has been modified and purified to limit innate immune activation. At the same time, the lipid nanoparticle (LNP) component was considered an inert carrier and protector of the mRNA. However, it has recently been shown that the synthetic ionizable lipid component of the LNPs is highly inflammatory...
The acute side effects reported with the mRNA-LNP vaccine platform are diverse and likely associated with its highly inflammatory nature...
Here, using an mRNA-LNP animal vaccination model, we show that pre-exposure to mRNA-LNP inhibits antibody responses. The inhibition could be overcome with the use of adjuvants, and did not interfere with the efficacy of protein vaccines. At the same time, however, this vaccine platform enhances innate immune fitness towards influenza infection but decreases resistance to Candida albicans. The enhanced immune fitness towards influenza can be passed down to the offspring...
Discussion
Based on our earlier studies demonstrating the pro-inflammatory properties of the LNP platform used in these vaccines, we report that pre-exposure to the mRNA-LNP platform has long-term impacts on both innate and adaptive immune responses, with some of these traits even being inherited by the offspring.
The first aim of our study was to assess whether a previous exposure to mRNA-LNPs influences the response to secondary vaccination. Interestingly, we found that indeed the antibody response was inhibited after an earlier administration of mRNA-LNPs. This inhibition of adaptive immune responses was relatively long-lasting, with effects seen for at least 4 weeks, and starting to wane after 8 weeks. Humans receive a 2-dose standard regimen of mRNA-LNP vaccines at 3 to 4 week intervals, and booster shots at different time points. Our data are strongly supported by recent studies showing that a delay of the second dose of an mRNA vaccine from 3 weeks to 3 months significantly improves the antibody response. Indeed, inflammation has been related to a poor responsiveness to vaccination in earlier studies, and it is rational to hypothesize that the acute inflammatory side effects of the LNP platform negatively impedes induction of antibody responses during the second dose administration. Increasing the interval between vaccination doses, thus giving time to the immune system to return to homeostasis, is likely to improve the effects of the second dose of the vaccine."
© 2022 Qin et al.
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