"1 Introduction
... [T]he 2 [Covid mRNA] vaccine types include different concentrations of mRNA per dose and have demonstrated differences in immunogenicity in different patient groups and between sexes assigned at birth. In addition, multiple studies have shown that the circulating vaccine induced antibody levels decline rapidly in most recipients within a couple of months of primary series vaccination, and the Centers for Disease Control and Prevention (CDC) has since recommended additional vaccination doses and vaccines to develop sustainable and effective humoral responses. To add complexity, new viral variants routinely emerge and often escape neutralization, resulting in high numbers of breakthrough infections...
In this proof-of-concept study, a 7,289-proteome assay was used to evaluate human protein markers pre- and post-homologous third dose of mRNA-1273 or BNT162b2 in healthy vaccine recipients and then the results were compared with humoral response. Specifically, serum antibodies to SARS-CoV-2 spike, proteins, and impacted cellular pathways were analyzed in samples collected 1-month and 6-months after a third dose of vaccine and compared to pre-third dose samples...
4 Discussion
... The SARS-CoV-2 mRNA vaccines are known to activate both adaptive and innate immune responses due to their complex nature. The lipid delivery systems of mRNA vaccines may have strong inflammatory effects, as lipid nanoparticles can be detected by TLR-4 and TLR-2. The RNA components could also trigger a variety of innate sentry sensors (TLR receptors) such as TLR-3, TLR-7, and TLR-8. Repetitive vaccination with mRNA vaccines may also have additional effects, as studies have demonstrated that repeated vaccinations can correlate with upregulation of dendritic cell activation and TLR signaling; BNT162b2 vaccination induces a moderate innate immune response that increases notably with subsequent vaccinations...
Sera from BNT162b2 vaccine cohorts, regardless of sex assigned at birth, showed upregulation of 3 common markers at 1-month post-third vaccination: UB2D1/PolyUbiquitin K48 (UBE2D1|UBB), Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), and Cancer/testis antigen 1 (CTAG1A|CTAG1B)... Cancer-testis antigen are [sic] identified in a variety of malignant tumors and are normally only expressed in testis tissues. However, testis antigens have been identified in cancer tissues in both male and female patients and can be a primary target of anti-cancer immune responses. To date, there are no searchable reports describing modulation of either Glutathione-specific gamma-glutamylcyclotransferase 1 proteins or cancer-testis antigens in sera associated with either SARS-CoV-2 infection or vaccination with either BNT161b2 or mRNA-1273."
© 2025 Hickey, Mudunuri, Hempel, Kemp, Roche, Talsania, Sellers, Cherry and Pinto.
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