Anti‐SARS‐CoV‐2 mRNA vaccines as inducers of humoral response against apolipoprotein A‐1?

Abstract

Background COVID‐19 and some anti‐SARS‐CoV‐2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients’ prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A‐1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID‐19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti‐SARS‐CoV‐2 mRNA‐based vaccination on AAA1 autoimmune biomarkers in RA patients. Methods 20 healthy controls and 77 RA mRNA‐based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS‐CoV‐2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded. Results mRNA‐based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol. Conclusions mRNA‐based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies.

Autoantibodies against apolipoprotein A‐1 after COVID‐19 predict symptoms persistence

“…Similarly, an increase in AAA1 IgGs has also been documented following COVID-19 mRNA vaccine. 41,42 Our results are in line with previous reports indicating that linear sequence between apoA-1 and other RNA viruses' epitopes, may underlie higher AAA1 IgG seropositvity rates observed in HIV, reaching 50% and being associated with surrogate biological markers of infection severity. 35 Similarly, HCV infection has been associated with an increase in AAA1 IgGs.…”

“…Extending previous investigations performed so far, 20 this the fourth independent cohort validating the proof of principle that SARS‐CoV‐2 infection increases the humoral response against apoA‐1. Similarly, an increase in AAA1 IgGs has also been documented following COVID‐19 mRNA vaccine 41,42 . Our results are in line with previous reports indicating that linear sequence between apoA‐1 and other RNA viruses’ epitopes, may underlie higher AAA1 IgG seropositvity rates observed in HIV, reaching 50% and being associated with surrogate biological markers of infection severity 35 .…”

BMI-Associated Anti-Apolipoprotein A-1 Positivity in Healthy Adults after mRNA-Vaccination against COVID-19

“…We did not document an association between mRNA vaccination and the transient AAA1+ rate, as suggested by a recent study [ 11 ]. However, different trajectories of AAA1 levels after vaccination were seen in overweight and obese subjects compared to those with a normal body weight.…”

“…Another approach to identifying potential risk factors (including mRNA vaccination) which could increase the occurrence of autoimmune disease, involves the search for certain markers or autoantibodies. A recent study hypothesizing about increased levels of anti-apolipoprotein A-1 antibodies (AAA1) after mRNA vaccination against COVID-19 in rheumatoid arthritis patients as well as in healthy adults was, in fact, based on similar outcomes reported in subjects after SARS-CoV-2 infection [ 11 , 12 ].…”

New insights into Covid‐19 disease. Apo‐A1 antibodies are generated after mRNA Covid‐19 vaccination and after Covid‐19 infection

“…In their manuscript, Vuilemier and colleagues 7 show a limited, but significant, presence of Apo-A1 antibodies (auto-antibodies against native and lipid-free apoA-1; AAA1 IgG) after anti-SARS-CoV-2 mRNA vaccines, after two successive vaccinations. As they already state, their study is observational in design (and in a small cohort) and therefore their observations should be understood as hypothesis-generating.…”