Vaccines for Autoimmune Diseases: Stopping Triggers, Restoring BalanceA Systematic Review with Qualitative Synthesis

To critically review the scientific background on vaccines designed to prevent autoimmune diseases, including two main strategies: (1) vaccines directed against pathogens involved in triggering disease, including Epstein-Barr virus (EBV), enterovirus and Streptococcus pyogenes; and (2) tolerogenic vaccine approaches targeting the immune response to restore tolerance to self-antigens.

We performed a thorough systematic review of clinical trials, observational studies, meta-analysis and pre-clinical data. A broad search was implemented in biomedical databases and gray literature. This systematic review was conducted with qualitative synthesis, given the heterogeneity of study designs, diseases, and outcomes. Two reviewers independently selected studies for inclusion and extracted data, using standard risk of bias and quality of evidence assessment tools.

There were 68 studies, 36 in humans and 32 preclinical studies included. In the anti-infective area, options include gp350 vaccine for EBV (phase 2), mRNA based early-stage vaccines, a population-based study of the impact of rotavirus vaccination on type 1 diabetes incidence, and inactivated PRV-101 Coxsackie B strain vaccine; for rheumatic fever, phase 1 trials are providing evidence with vaccines such as StreptAnova and J8/S2. With regard to the tolerogenic line, tolerogenic DC-based and of myelin peptides vaccines have shown immune regulation in illnesses such as MS and RA, but do not yet demonstrate solid clinical evidence.

Trigger infections vaccines are now nearing clinical use whereas tolerogenic vaccines constitute an attractive approach for the future. The combination of these approaches has the potential to inform future preventive and therapeutic strategies, but current evidence remains heterogeneous and largely early-stage, particularly for tolerogenic platforms.