"4. Discussion
... [W]e investigated the specific humoral effects of the BNT162b2 vaccine developed by BioNTech/Pfizer, as well as its effects on the innate immune responses to various viral, bacterial, and fungal pathogens. We show that the BNT162b2 vaccine induces long-term effects on both adaptive and innate immune responses, including transcriptional changes and effects on cytokine production capacity.
... [W]e observed a decline in antibody concentrations and neutralizing capacity six months after vaccination. It has been hypothesized that this decline is likely caused by plasmablasts that do not differentiate into long-lived memory plasma cells. Booster vaccination restored the antibody concentrations, even higher than the concentrations after the first vaccination cycle. However, this increase was not significant...
The lack of neutralizing capacity against the omicron variant after six months raises significant concerns, a finding also reported by others. Omicron strains are, at the moment of writing, the most prevalent circulating variants, characterized by large numbers of mutations in the spike protein. Those mutations, together with a recently detected higher affinity for the receptor angiotensin-converting enzyme 2 (ACE2), are suspected to be the reason why omicron variants so effectively escape antibody recognition...
Mouse models have pointed out the inflammatory feature of the LNP-delivered and modified-mRNA components of BNT162b2, however, from these studies it remains unclear how long this inflammatory state persists. While it is known that chronic inflammation can result in, for instance, T-cell exhaustion, future larger studies should assess any potential long-term inflammatory effects of mRNA vaccines in humans...
More remarkable is... the tendency of lower interferon responses after BNT162b2 vaccination... [W]e observed a downregulation of the type I interferon pathway in response to influenza at the transcriptional level, and lower IFN-α production by PBMCs [peripheral blood mononuclear cells] after stimulation with SARS-CoV-2. A similar pattern can be observed for IFN-γ, which was produced less by PBMCs after immunization when exposed to various viral stimuli...
Recently, some debate has been ongoing on whether immunization with an mRNA COVID-19 vaccine is associated with the reactivation of latent viral diseases, such as human herpes viruses and hepatitis C virus. Possible explanations include the suppression of specific CD8+ cells by the immense shift of naïve CD8+ cells after immunization and the downregulation of TLR [toll-like receptor] pathways through immunization and thereby inhibiting of interferon production. The hypothesis of downregulated interferon production agrees with our data... Our ex-vivo results offer a potential explanation for the observation reported in several studies that have suggested a correlation between an increased number of prior vaccine doses and higher risk of contracting... It may be thus hypothesized that vaccination with mRNA-based vaccines causes dysregulation of innate immune responses, and that the consequences of this effect for protection against SARS-CoV-2 cannot be fully compensated by the induction of adaptive immune responses."
© 2023 The Authors. Published by Elsevier Inc.
This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
You are not required to obtain permission to reuse this article.