0787: Relationship Between Humoral and Cellular Immune Responses in Persons with Rheumatoid Arthritis Following a Third Dose of COVID-19 Vaccine

Sara Tedeschi¹, Daniel Solomon¹, Yuezhou Chen², Jack Ellrodt¹, Mary Grace Whelan¹, Jacklyn Stratton¹, Keigo Hayashi³, Noah Whiteman², Lin Chen¹, Ifeoluwakiisi Adejoorin¹, Kathryne Marks¹, Emma Gomez-Rivas¹, Deepak Rao¹, Anna Jonsson¹ and Duane Wesemann², ¹Brigham and Women's Hospital, Boston, MA, ²Harvard Medical School, Boston, MA, ³Brigham and Women's Hospital, Okayama, Japan

Background/Purpose: DMARDs that treat RA may reduce immune responses to COVID-19 vaccination. We compared measures of humoral and cell-mediated immunity in RA patients before and after a 3rd dose of COVID-19 vaccine.

Methods: RA patients that had previously received 2 doses of mRNA vaccine enrolled in a single-center prospective observational study, July-Dec 2021, before receiving a 3rd dose of mRNA vaccine. Subjects self-reported holding or continuing DMARDs; rituximab users were excluded from analysis. RA disease activity (RADAI-5) was self-reported weekly pre- and post-3rd dose. Blood samples were collected pre- and week 4 post-3rd dose. Humoral response was measured with in-house ELISA assays for anti-Spike (anti-S) and anti-receptor binding domain (anti-RBD) IgG in equivalent units to monoclonal antibody positive control; results were log-transformed prior to statistical analyses. We calculated delta and fold-change of anti-S and anti-RBD post- vs. pre-3rd dose. "Healthy response" to the 3rd dose was defined as ELISA within 1 standard deviation of the mean among 6 healthy controls 4-8 weeks after a 2nd dose of mRNA vaccine. Cell-mediated response was assessed in a subset of seropositive RA subjects by incubating PBMCs with SARS-CoV-2 peptide pool (Miltenyi Biotec). Adjusted frequencies of stimulated CD4 T cells expressing < ![if !msEquation] >< ![if !vml] >< ![endif] >< ![endif] >2 activation markers (IFNg, TNF, IL-2, 4-1BB, CD40L, CD69) were compared pre- vs. post-3rd dose. Spearman's correlations assessed the relationship between ELISA levels and frequencies of activated CD4 T cells. Subgroup analyses compared subjects (a) holding vs. continuing DMARDs and (b) by DMARD group.

Results: Among 60 subjects, mean age was 63 and 88% were female. TNFi (43%) and methotrexate (23%) were the most common DMARDs (Table 1). 57% held at least 1 DMARD around the 3rd dose; baseline RA disease activity did not significantly differ between those holding vs. continuing DMARDs (p=0.58). At week 4 post-3rd dose, a "healthy response" was observed in 38% for anti-S and 45% for anti-RBD. Anti-S ELISA levels increased 1.4-fold among those holding DMARDs and 1.5-fold among those continuing DMARDs (p=0.56); anti-RBD increased 1.6-fold in those holding DMARDs and 1.7-fold in those continuing DMARDs (p=0.76) (Figure 1). Fold-change in anti-S and anti-RBD ELISA were similar when comparing methotrexate to other DMARD groups (p >0.05 for each comparison). Among 26 subjects that provided PBMCs, frequencies of activated CD4 T cells were significantly greater post- vs. pre-3rd dose in both those that held DMARDs (p< 0.01) and those that continued DMARDs (p=0.02) (Table 2). Neither fold-change nor delta ELISA level was significantly correlated with the change in frequency of activated CD4 T cells (rho -0.26 to -0.06, p >0.05).

Conclusion: After a 3rd dose of mRNA COVID vaccine, ELISA levels significantly increased in RA subjects using DMARDs though fewer than half achieved a humoral response on par with healthy controls after a 2nd dose. Change in ELISA levels did not correlate with CD4 T cell responses. Additional studies are needed to determine clinical relevance of quantitative differences in humoral and cell-mediated responses in immunosuppressed patients.





Disclosures: S. Tedeschi, Moderna, NGM Biopharmaceuticals; D. Solomon, AbbVie/Abbott, Amgen, moderna, CorEvitas; Y. Chen, None; J. Ellrodt, None; M. Whelan, None; J. Stratton, None; K. Hayashi, None; N. Whiteman, None; L. Chen, None; I. Adejoorin, None; K. Marks, None; E. Gomez-Rivas, None; D. Rao, Janssen, Merck, Bristol-Myers Squibb, Scipher Medicine, HiFiBio, Inc., AstraZeneca, Pfizer; A. Jonsson, Amgen; D. Wesemann, None.