Vaccination in the Era of Immunosuppression

Abstract

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for severe infections. Vaccine responses and safety profiles may differ between AIIRD patients and the general population. While patients with autoimmune inflammatory rheumatic diseases (AIIRDs) often experience diminished humoral responses and reduced vaccine efficacy, factors such as the type of immunosuppressant medications used and the specific vaccine employed contribute to these outcomes. Notably, individuals undergoing B cell depletion therapy tend to have poor vaccine immunogenicity. However, despite these considerations, vaccine responses are generally considered clinically sufficient. Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, it is common for many patients to already be on immunosuppressants during the immunization process. Vaccination rarely triggers flares in AIIRDs; if flares occur, they are typically mild. Despite the heightened infection risk, including COVID-19, among AIIRD patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other diseases on immunosuppressants, the vaccination rates remain suboptimal. The future directions of vaccination in the era of immunosuppression will likely involve customized vaccines with enhanced adjuvants and alternative delivery methods. By addressing the unique challenges faced by immunosuppressed individuals, we may improve vaccine efficacy, reduce the risk of infections, and ultimately enhance the health outcomes. Additionally, clinical trials to evaluate the safety and efficacy of temporarily discontinuing immunosuppressants during vaccination in various AIIRDs are crucial.

Keywords: autoimmune; immune response; immunosuppressed; vaccination.

Figure 1

Immune response to vaccination. Once administered, the vaccine particles are phagocytosed by the innate immune system’s antigen-presenting cells (APCs). These cells process the engulfed particles and subsequently present the antigens to adaptive immune system cells. The presentation of antigens by APCs depends on the type of vaccine-incorporated components (i.e., protein subunit with or without a protein-bound adjuvant, viral DNA or mRNA vaccine, viral particles, viral or bacterial live attenuated vaccines, etc.). In general, viral antigens are presented on major histocompatibility complex type (MHC)-1 peptides to cytotoxic CD8+ T cells to activate cell-mediated immunity and viral host defense through the release of cytotoxic mediators (mainly perforin and granzyme). Bacterial and parasitic antigens are presented on MHC-2 peptides to CD4+ T cells that stimulate effector and memory T cell responses. Follicular T cells (TFH cells) aid in B cell activation and differentiation into plasma cells, which produce antigen-specific high-affinity antibodies. B cell activation may also be independent of T cells through direct interaction with the vaccine particles or through interaction with an APC. The inherent function of the APCs, T cells, and B cells involved in the immune response to vaccine may be altered by the presence of AIIRDs and the use of immunosuppressive therapy.