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Global Translational Medicine Autoimmune diseases after vaccination

Table S2 illustrates reporting bias values (r ) of 1/20 and to elasomeran vaccines (Figure 3) suggest that increasing
0
1/40; however, based on the frequency of VAERS reports the time between first and second doses for this vaccine
related to common adverse events of COVID-19 vaccines, to at least 4 weeks or longer would likely decrease the dose
the r (URF) for these vaccines (Equation VIII) could be 2 to dose 1 ratio, as observed in Figure 3. This extended
0
closer to 1/241. If r is indeed close to 1/241, then many of interval is predicted to help mitigate higher non-specific
0
the detected COVID-19 ADAEs (Table S1) hold significant. amplification observed for the tozinameran COVID-19
vaccine when the second dose is administered just 3 weeks
Primary and secondary humoral immune responses,
with the amplification of B-cell antibodies, increase over a after the first dose (Figure 3).
period of multiple days (peaking around 7- – 11-day post- These COVID-19 vaccines appear to induce immediate-
immunization). Observed ADAEs (Table S1) that occur onset ADAEs, which are consistent with subsets of at-risk
within 24 h after immunization cannot be attributed to vaccinees exceeding the disease onset thresholds for
either primary or secondary humoral immune responses a broad spectrum of autoimmune diseases (Table S1).
(the immediate timespan is inconsistent with humoral Based on the onset data reported in VAERS, the highest
immune responses). Immediate ADAEs are more risks appear to be immediately post-immunization,
consistent with the hypothesis of autoimmune disease especially for at-risk vaccinees. By design, both mRNA and
threshold being exceeded due to immune dysregulation on adenoviral vaccine platforms elicit high levels of expression
a rapid timescale post-immunization. of the SARS-CoV-2 spike protein, which is foreign to the
immune systems, effectively stimulating strong immune
4.1. COVID-19 mRNA and adenoviral vaccines responses. COVID-19 ADAEs associated with 33
Most COVID-19 vaccines available on the market are the autoimmune diseases/groups are summarized in Table S1.
novel mRNA and adenoviral vaccines, and both of these The observed patterns of immediate-onset frequencies,
vaccine platforms have been associated with multiple common to all ADAEs (Figures 1 and 2, Table S1), suggest
ADAE (Table 1). For both Ad26.Cov2.S and tozinameran the possibility of unintended immune responses triggering
vaccines, the percentage of associated ADAE is higher these ADAEs. These frequency patterns are consistent with
than the elasomeran vaccine. For instance, for the Ad26. the hypothesis of bystander or polyclonal activation but
[2]
Cov2.S vaccine, GBS accounts for 16.2% of the adverse not epitope molecular mimicry (as there is insufficient
events but represents only 3.1% of the COVID-19 vaccine time for adaptive immune responses to vaccine epitopes).
[15]
doses (Table 1). All three of these COVID-19 vaccines Note that Guo et al. have considered molecular mimicry,
contribute to the combined COVID-19 results reported adjuvants, and bystander activation. In examining the
in Table S1. Of particular note is the high percentage of etiology of COVID-19 vaccine ADAEs, Table S1 presents
Bell’s palsy occurrence when compared to other vaccines data on 33 different autoimmune diseases with immediate
(Table S1). In comparison to widely provided vaccines onset, indicating an immediate effect rather than a direct
result of the expressed spike protein or possible shared
like influenza and others, COVID-19 immunizations epitopes. Differences in age distributions among vaccinees
show a broad association with many autoimmune diseases
(Table S1). Furthermore, high percentages of these ADAEs for selected autoimmune diseases are illustrated in
are reported within 24 h of immunization (Table S1). Figure 4. The demographic characteristics of individuals
experiencing these ADAEs are consistent with the
The timing of mRNA vaccine doses appears to be amplification of pre-existing mechanisms, especially for
important for ADAE onset (Figure 3). Specifically, the individuals at higher risk of developing these autoimmune
tozinameran mRNA COVID-19 vaccine exhibits a higher diseases. For instance, polymyalgia rheumatica, one of the
number of ADAE reports for 30 out of 32 autoimmune COVID-19 ADAEs, is predominantly reported in older
adverse events for dose 2 compared to dose 1, with a ratio adults (Figure 4).
[29]
>1.0. In 29 of these cases, the ratio >1.1, with Bell’s palsy
being the only exception (ratio = 0.79) (Figure 3). On the 4.2. HPV vaccines
other hand, the elasomeran mRNA COVID-19 vaccine The HPV vaccines contain aluminum as an adjuvant .
[3]
shows seven vaccines with ratios >1.0 and three vaccines While aluminum has a long history of use in vaccines,
>1.1. Notably, the elasomeran vaccine contained 100 it is also associated with neurotoxicity [3,22] . In mice,
micrograms of mRNA, with 4 weeks between the first and macrophages have been shown to transport aluminum
second vaccine doses, whereas the tozinameran vaccine to lymph nodes, spleen, liver, and brain . Regarding
[30]
contained 30 μg of mRNA, with only 3 weeks between the correlation of HPV vaccines with adverse events, it
the first and second vaccine doses. The higher ADAE is noteworthy that temporal onset correlations exist with
ratios observed for the tozinameran vaccine compared multiple ADAEs (Table S1). Among these, the ADAEs with

Volume 2 Issue 3 (2023) 6 https://doi.org/10.36922/gtm.1455