1. Molecular MimicryMolecular mimicry occurs when antigens produced by the mRNA vaccine resemble self-antigens, leading to cross-reactive immune responses that attack host tissues.Mechanism: The SARS-CoV-2 spike protein, encoded by mRNA vaccines, may share structural or sequence similarities with human proteins. If T cells or antibodies generated against the spike protein cross-react with self-antigens, this could initiate autoimmune responses.

2. Epitope SpreadingEpitope spreading refers to the broadening of immune responses from vaccine-induced antigens to unrelated self-antigens, amplifying autoimmune damage.Mechanism: Initial immune activation against the spike protein may cause tissue damage, releasing self-antigens. These newly exposed self-antigens stimulate additional immune responses, perpetuating autoimmunity.

3. Bystander ActivationBystander activation involves non-specific activation of autoreactive immune cells during a robust immune response to the vaccine.Mechanism: mRNA vaccines induce strong innate immune responses via lipid nanoparticles (LNPs) and mRNA, activating Toll-like receptors (TLRs) and releasing pro-inflammatory cytokines (e.g., IL-6, TNF-α). This inflammatory milieu can activate dormant autoreactive T or B cells, leading to autoimmunity.

4. Adjuvant Effects of Lipid Nanoparticles (LNPs)LNPs, used to deliver mRNA, act as adjuvants, enhancing immune responses but potentially overstimulating the immune system.Mechanism: LNPs activate innate immunity through pathways like TLR7/9, promoting inflammation and cytokine production. Excessive or prolonged activation may disrupt immune tolerance, enabling autoreactive responses.