Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients

Abstract

Importance: Data on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. Objective: To determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. Design: Retrospective observational cohort study. Setting: Large healthcare system in Northern California. Participants: This study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s): Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s): Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results: 496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (n=48, P<.001), sphingosine 1-phsophate (S1P) receptor modulators (n=11, P<.001), mycophenolate (n=78, P=.002), and B cell lymphoma (n=55, P=.004); those associated with low rates of cellular response included S1P receptor modulators (n=11, P<.001) and mycophenolate (n=69, P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and Relevance: Cellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

“…Our main finding is, thus, that after a third dose of SARS-CoV-2 mRNA vaccines, only a subset of patients mounts a humoral immune or CMI response. Emerging reports by others have found a similar rate of around 25% de novo antispike seroconversion after a third dose of SARS-CoV-2 vaccines in patients on anti-CD20 therapies that were humoral non-responders after a two-dose vaccination scheme 8–10 18–23. Several studies that used EliSpot or activation-induced markers to semiquantitatively assess CMI revealed higher rates of CMI than humoral responses after a third SARS-CoV-2 vaccine in patients with autoimmune diseases under anti-CD20 treatment 8 19 24–26.…”

Booster COVID-19 Vaccines for Immune-Mediated Inflammatory Disease Patients: A Systematic Review and Meta-Analysis of Efficacy and Safety

“…The screening process is illustrated in the PRISMA flowchart in Figure 1 . Of these studies, there were 12 observational studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], one randomised-controlled trial [ 33 ], and four case series [ 34 , 35 , 36 , 37 ]. The key trial characteristics of each included study are reported in Table 1 , with a comparison of the characteristics of the studies included in the meta-analysis in Table S2 .…”

“…COVID-19 booster vaccines administered in the studies included mRNA (Pfizer-BioNTech, BNT162b2 and Moderna, mRNA-1273) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 34 , 35 , 36 , 37 ], non-replicating viral vector (AstraZeneca, AZD1222 and Janssen, Ad26.COV2.S) [ 21 , 28 , 29 , 30 , 34 , 35 , 36 , 37 ], protein subunit (Novavax, NVX-CoV2373) [ 33 ] and inactivated (Sinovac, CoronaVac) vaccines [ 35 ]. Bonelli et al involved two cohorts receiving mRNA vaccines as the primary series, but one received heterologous AstraZeneca booster doses while the other received homologous mRNA boosters [ 29 ].…”

Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework

“…In 1 study, use of immunosuppression in patients with autoimmune disease resulted in 1. 35-fold (95% CI, 1.29-1.40) greater odds of developing life-threatening .…”