Humoral SARS-CoV-2 immunogenicity wanes 3 months after heterologous inactivated vaccine followed by ChAdOx1 nCoV-19 in autoimmune rheumatic diseases.

BACKGROUND: Alongside vaccine hesitancy, impaired and waning immunity in autoimmune rheumatic diseases (ARDs) are barriers to immunization. The timeframe of immunity waning in ARD remains unclear. OBJECTIVE: We aimed to examine the waning of humoral immunogenicity in a cohort of ARD patients who received the heterologous inactivated vaccine followed by the adenoviral vector SAR-CoV-2 vaccine at a 3-month follow-up. METHODS: The levels of SARS-CoV-2 anti-RBD IgG were evaluated at 1 and 3 months in adults with ARDs (n = 29) and age- and sex-matched healthy controls (HC) that received the heterologous prime-boost CoronaVac vaccine followed by the ChAdOx1 nCoV-19 vaccine. Seropositivity was defined as anti-receptor binding domain (RBD) IgG levels of ≥ 7.15 binding antibody units (BAU)/mL. The kinetic properties of the vaccines were evaluated based on the ratio of anti-RBD IgG values obtained at each follow-up. Disease activity was evaluated. RESULTS: The seropositivity rate was lower among patients with ARDs than among HCs (89.7% vs. 100%, p = 0.237). At 3 months, the median (IQR) anti-RBD IgG level was lower among patients with ARDs than among HCs (122.3 [30.6, 247.8] vs. 294.2 [127.4,605.7] BAU/mL, p = 0.006). Mean antibody levels in patients with ARDs decreased 3.5 (1.9)-fold within 3 months post-vaccination (122.3 [30.6, 247.8] vs. 279.9 [86,1076.5] BAU/mL, p < 0.001). Disease flare-ups occurred in three patients. CONCLUSIONS: Our findings included changes to anti-RBD IgG levels and may inform vaccination strategies. SAR-CoV2 vaccine-induced immunity was lower in patients with ARDs than in HCs and decreased within 3 months, suggesting a need for booster vaccinations.

Impaired neutralizing antibodies and preserved cellular immunogenicity against SARS-CoV-2 in systemic autoimmune rheumatic diseases.

Reports on vaccine immunogenicity in patients with systemic autoimmune rheumatic diseases (SARDs) have been inconclusive. Here, we report the immunogenicity of heterologous prime-boost with an inactivated vaccine followed by an adenoviral vector vaccine in patients with SARDs using anti-RBD antibodies, neutralizing capacity against Omicron BA.2 [plaque-reduction neutralization test (PRNT)], T cell phenotypes, and effector cytokine production at 4 weeks after vaccination. SARD patients had lower median (IQR) anti-RBD-IgG levels and neutralizing function against the Omicron BA.2 variant than the healthy group (p = 0.003, p = 0.004, respectively). T cell analysis revealed higher levels of IFN-γ- and TNF-α-secreting CD4 + T cells (p < 0.001, p = 0.0322, respectively) in SARD patients than in the healthy group. Effector cytokine production by CD8 + T cells was consistent with Th responses. These results suggest that this vaccine regimen revealed mildly impaired humoral response while preserving cellular immunogenicity and may be an alternative for individuals for whom mRNA vaccines are contraindicated.