In a recent article published in Nature Communications, researchers investigated whether messenger ribonucleic acid (mRNA) technology-based coronavirus disease 2019 (COVID-19) vaccines promote the development of autoantibodies.
Previous studies have found an association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and autoantibody development. While some of these reactivities were preexisting, the scientists noted some novel ones coinciding with infection onset.
SARS-CoV-2 mRNA vaccines elicit rapid immune response preventing symptomatic coronavirus disease 2019 (COVID-19) and severe disease. In some cases, they also elicit common flu-like symptoms and myocarditis. Patients with preexisting autoimmune diseases are particularly at risk of adverse after-effects of COVID-19 vaccines.
More recently, scientists have also raised concerns that molecular mimicry by SARS-CoV-2 spike (S) protein might be helping elicitation of vaccine-driven humoral autoimmunity. Moreover, studies have barely explored whether autoantibody responses after vaccination varied from case to case, e.g., among previously infected relative to SARS-CoV-2 naïve individuals.
About the study
In the present study, researchers used Rapid Extracellular Antigen Profiling (REAP), an autoantibody screening platform, to demonstrate that autoantibodies are stable post-vaccination compared to acute COVID-19.
It helped the researchers quantify antibody responses against the SARS-CoV-2 receptor binding domain (RBD) and some extracellular antigens. In addition, it helped them assess antibody reactivity against 6183 extracellular proteins and peptide epitopes found in humans.
They characterized self- and SARS-CoV-2-directed humoral immune responses after mRNA COVID-19 vaccination in 38 autoimmune patients, 145 healthy individuals, and eight patients with vaccine-related myocarditis.
The Benaroya Research Institute (BRI) recruited the autoimmune disease cohort and had 25 healthy controls besides 38 autoimmune patients. Of these 38 patients, 13, 13, one, one, and one patients had multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and Crohn’s disease (CD), respectively. Further, the team performed an enzyme-linked immunosorbent assay (ELISA) on individuals comprising the BRI cohort. Finally, the team analyzed REAP data from 36 moderately and 23 severely ill COVID-19 patients.
Nearly 50% of severely and one-third of moderately ill COVID-19 patients had a minimum of one new or increased autoantibody reactivity, with many having multiple reactivities. On the contrary, this was immensely rare post-vaccination. Accordingly, of 1034 autoantibody reactivities observed in the vaccine cohort, only 15 were new. Among acute COVID-19 cases, of 463 autoantibodies, only 24 were new, i.e., 5.18%.
The REAP most sensitively detected new autoantibodies over time. Accordingly, it captured a surge in REAP score for tumor necrosis factor-alpha (TNFα) in a Rheumatoid Arthritis (RA) patient on adalimumab monoclonal antibody therapy in the period of collecting pre and post-vaccination samples.
In the COVID-19 cohort, higher age, female sex, and disease severity score of six increased the magnitude of increased autoantibody reactivities. However, the same did not happen in the vaccine cohort. The vaccine cohort showed no apparent pattern of new or increased autoantibody reactivities, even in autoimmune-susceptible individuals.
Patients in the cohort comprising vaccine-induced myocarditis did not exhibit surge autoantibodies relative to controls. Moreover, they did not have autoantibodies against cardiac enriched antigens associated with cardiac inflammatory disease states, e.g., anti-B adrenoreceptor antibodies.
Intriguingly, the authors did not detect interleukin-1 receptor antagonist (IL-1Ra) autoantibodies in the study cohort by REAP or ELISA. This discrepancy with other recent reports most likely occurred because these reports did not note whether patients received anti-drug antibodies against IL-1RA.
The Centers for Disease Control and Prevention (CDC) recommends a third and fourth mRNA vaccine dose for immunocompromised individuals receiving therapies, including patients with autoimmune diseases.
In this regard, the current study results showed that these patients generated SARS-CoV-2 RBD-specific antibodies post-vaccination, but their antibodies were mostly non-neutralizing, distinct from those generated by healthy individuals. Clearly, their anti-SARS-CoV-2 antibody response was limited and less effective. It targeted non-critical epitopes or lacked anti-N-terminal-domain (NTD) antibodies, especially in individuals on B cell reduction therapies. In this study, the authors did not quantify T-cell responses to COVID-19 mRNA vaccination, which implies they failed to infer the extent of immune protection against SARS-CoV-2.
Though most of the study population exhibited strong SARS-CoV-2-specific antibody responses post-vaccination, autoimmune patients showed an impaired response quality-wise on specific immunosuppression modes. Patients with vaccine-induced myocarditis did not have increased autoantibody reactivities.
However, compared to COVID-19 patients that exhibited an increased prevalence of novel autoantibody reactivities, all vaccinated patients showed stable autoantibody dynamics. The study showed that mRNA COVID-19 vaccines decoupled SARS-CoV-2 immunity from autoantibody responses previously detected during acute COVID-19.