Humoral Response to 3rd Dose Sars-Cov-2 Vaccine in Patients with Idiopathic Inflammatory Myopathies

Background. Vaccine-induced SARS-CoV-2 antibody responses are reduced in patients taking lymphocyte-depleting therapies, which are commonly prescribed for patients with idiopathic inflammatory myopathies (IIM). While a third vaccine dose (D3) augments the SARS-CoV-2 anti-spike response in some patients, there is a paucity of data on the humoral response following D3 in patients with IIM. Furthermore, the durability of antibody response is unknown. In this study, we evaluated serial antibody response for three months following a 3rd dose SARS-CoV-2 vaccination in IIM patients. Methods. Adults with a patient-reported diagnosis of idiopathic inflammatory myopathy who completed three-dose SARS-CoV-2 vaccination (two-dose BNT162b2 or mRNA-1273 followed by single mRNA or adenoviral vector dose) were recruited via social media campaign. Demographics and clinical characteristics were collected via patient report. Informed consent was provided electronically. Serial antibody responses were evaluated by the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures total antibody to the SARS-CoV-2 S-receptor binding domain (RBD) protein (range 0. 4-2500U/ mL;positive >0.8U/mL). Poor antibody response was defined as anti-RBD titer <500U/mL based on predicted correlates of protective plasma neutralizing capacity. Those with prior COVID-19 infection were excluded. Associations were evaluated using Fisher's exact and Wilcoxon rank-sum tests as appropriate. Results. We evaluated serial anti-RBD titers in 59 participants (Table I). Most (93%) were female with median (IQR) age of 51 (41-62) years. Mycophenolate mofetil was the most frequently prescribed medication (45.6%). Participants completed primary vaccination with two-dose BNT162b2(54%) or mRNA-1273(46%). Median pre-D3 anti-RBD titer (IQR) was 65.8U/mL (4.6,473) at 158 (136-183) days following primary vaccination. Dose 3 included BNT162b2(47%), mRNA-1273(47%) or Ad.26.COV2.S (6%). Most (89.9%) received homologous D3 vaccination. 39% of participants reported holding peri-D3 immunosuppression with mycophenolate mofetil being the most commonly held medication in the peri-D3 period. Repeat anti-RBD testing was performed at a median (IQR) 30 (28-32) days post-D3. A higher antibody titer was seen in 89.9% participants following D3 with median (IQR) titer of 2500 U/mL (92,2500). Thirty-seven percent remained <500U/mL following D3;a greater proportion of these participants reported use of rituximab and greater number of immunosuppressive therapies compared to those with anti-RBD >=500U (72.7% versus 5.4%, p<0.001;3 therapies versus 2 therapies, p=0.03). Furthermore, 13.5% (8/59) remained below the threshold of positivity following D3;7/8 reported use of rituximab, 5/8 mycophenolate mofetil, or combination of these agents (4/8). There was not a significant difference in antibody titers among recipients of homologous/heterologous vaccination (p=0.22). Dose 3 was well tolerated with only 2 (3.4%) participants reporting disease flare requiring treatment within one month of vaccination;neither required intravenous therapy or hospital admission. Thirty-four (57.6%) participants underwent repeat anti-RBD testing three months following D3 with median (IQR) 2500U/mL (456,2500);73.53% (25/34) remained above threshold of >=500U/mL. Limitations of this study include small sample size and absence of healthy control group. Diagnosis was based on participant report and we did not routinely collect information on disease activity. Conclusion. We observed an augmented humoral response in most IIM patients following 3rd dose SARS-CoV-2 vaccination;antibody response was durable at three months. Dose 3 was well tolerated. Over 1/3 participants failed to develop adequate response following D3, namely those on rituximab therapy and on higher number of immunosuppressive therapies. These patients should be prioritized for prophylactic therapies to enhance protection against COVID-19 infection.

Sars-CoV-2 Antibody Response Before and After Third Dose of Homologous mRNA Vaccine in Liver Transplant Recipients

Purpose: Liver transplant (LT) recipients have a decreased response to 2 doses of SARS-CoV-2 vaccine compared to the general population, so we aimed to understand response to a third dose to inform vaccination strategies. Method(s): LT recipients in our observational cohort who received 3 homologous mRNA vaccines and available antibody levels pre- and post-dose 3 (D3) were identified. Those who reported a prior COVID-19 diagnosis or used belatacept were excluded. The peak anti-spike antibody level collected between the second (D2) and third dose (D3), was compared to the antibody level at 1 month post-D3. Samples were tested with Roche Elecsys Anti-Sars-CoV-2 enzyme immunoassay (EIA) (positive >=0.8 U/mL) or EUROIMMUN EIA (positive >=1.1 AU). Result(s): 146 participants completed 3 homologous doses of BNT162b2 (53%) or mRNA-1273 (47%) vaccines between 5/15/2021 - 11/8/2021. The median (IQR) time of peak pre-D3 antibody collection was 89 (31, 104) days post-D2. The median time of 1-month post-D3 antibody collection was 30 (23, 33) days. The median time between D2 and D3 was 168 (149-188) days. Overall, 125/146 (86%) were seropositive pre-D3, and 139/146 (95%) were seropositive post-D3 (Figure 1). There were no seroreversions post D3, and among the 21 seronegative recipients pre-D3, 14 (67%) seroconverted post-D3. Risk factors significantly associated with persistent seronegativity post-D3 were less time since LT (1.3 vs 6 years, p=0.042), mycophenolate use (100% vs 37%, p=0.001), BNT162b2 series (100% vs 50%, p=0.01), and pre-D3 seronegative status (86% vs 10%, p<0.001). Conclusion(s): Most LT recipients have excellent responses to a third homologous mRNA vaccine dose, greater than that seen in other transplant recipients. Persons seronegative after D2, however, show weaker response and may remain at high risk for SARS-CoV-2 infection despite D3.

SARS-CoV-2 Antibody Response by mRNA Vaccine Platform in Incrementally Immunosuppressed Patients

Purpose: This study compares SARS-CoV-2 antibody responses between the twodose mRNA-1273 and BNT162b2 vaccine series across groups of incrementally immunosuppressed patients. Method(s): Semiquantitative testing for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was performed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA), 15-45 days after the second vaccine dose for SARS-CoV-2 naive patients with rheumatic and musculoskeletal disease (RMD), and solid organ transplant recipients (SOTRs) from an observational cohort. Anti-RBD titers were divided into categories of >=50, >=100 and >=250 U/mL based on levels associated with plasma neutralizing capacity in COVID-19 convalescent patients. Participants were stratified by increasing intensity of immunosuppression: RMD not on immunosuppression, RMD on immunosuppression, SOTR not on mycophenolate (MMF), and SOTR on MMF. Response rates between mRNA-1273 and BNT162b2 recipients were compared using modified Poisson regression weighted for age, time since vaccination, and number of immunosuppressive medications. This analysis was repeated for several thresholds of positive response: 50, 100, and 250 U/mL. Result(s): Of 1868 participants, 55.8% of RMD and 52.7% of SOTRs received BNT162b2;the remainder received mRNA-1273. Demographics, diagnoses, and immunosuppressive regimens were similar across vaccine groups. Among RMD participants not on immunosuppression, the chance of anti-RBD >=250U/ml was comparable among BNT162b2 and mRNA-1273 recipients (IRR= 0.91 1.03 1.16 p= 0.67). mRNA-1273 recipients had a higher chance than BNT162b2 recipients to achieve anti-RBD >=250U/ml among RMD participants on immunosuppression (IRR = 1.15 1.241.34, p<0.001);SOTRs not on MMF (IRR = 1.24 1.561.96, p <0.001);and SOTRs on MMF (IRR=1.28 2.625.37, p= 0.01). Similar trends were observed with titer cutoffs of >=100 and >=50 U/mL (Table 1). Conclusion(s): The two-dose mRNA-1273 vaccine series was more likely to induce stronger humoral immunogenicity compared to BNT162b2 in immunosuppressed patients;this effect was more pronounced with greater immunosuppression. These findings suggest importance in the choice of mRNA vaccine platform in optimizing immune responses to SARS-CoV-2 vaccination and can help inform vaccination strategies for booster doses in high-risk, immunosuppressed populations.

Humoral and Cellular Immune Response to a Third Dose of SARSCoV- 2 Vaccine in Kidney Transplant Recipients on Belatacept

Purpose: Kidney transplant recipients taking belatacept (KTR-B) have poor immune response to two-dose SARS-CoV-2 vaccination. We sought to characterize the impact of an additional vaccine dose on plasma neutralizing capacity and cellular responses as compared to that of KTRs controls (KTR-C) not taking belatacept. Method(s): Within an observational cohort, we tested 26 KTR-Bs and 27 KTR-Cs for anti-spike antibody responses before and after a third SARS-CoV-2 vaccine dose (D3) using two clinical assays (Roche Elecsys anti-S Ig and EUROIMMUN anti-S1 IgG). For a subset of 5 KTR-Bs and for all KTR-Cs we used a research assay (Meso Scale Diagnostics V-Plex [MSD]) to further assess anti-spike and RBD IgG, as well as surrogate plasma neutralizing activity (% ACE2 inhibition) versus the ancestral and delta variants. For 3 KTR-Bs, post D3 T cell response was assessed via IFN-y ELISpot and deemed positive if spot forming units > 20 per million PBMC and stimulation index > 3. Result(s): KTR-Bs had significant lower clinical anti-spike seroconversion than KTR-Cs (31% vs 74%, p=0.001) after D3 despite similar demographics, clinical factors, and vaccines administered (Table 1). No KTR-B (0/5) was seropositive by MSD anti-spike or anti-RBD IgG (Figure 1). % ACE2 inhibition versus the ancestral variant was significantly lower in KTR-Bs than in KTR-Cs (Median [IQR] 5.2 [2.8, 6.5] vs 12.5 [7.7, 23.9], p<0.01);all KTR-Bs were below a level consistent with detectable neutralizing antibody. All tested KTR-Bs (3/3) had a negative ELISpot, consistent with negligible cellular response. Conclusion(s): These results suggest minimal humoral or cellular immunogenicity of additional vaccine doses for KTR-Bs and indicates the need for alternative strategies to improve vaccine response such as immunosuppression alteration or use of passive immunoprophylaxis with monoclonal anti-spike antibody to improve protection versus SARS-CoV-2.

Pre-Vaccine Antibodies Against Seasonal Betacoronaviruses Are Associated with Decreased Antibody Response to SARS-CoV-2 mRNA Vaccination in Solid Organ Transplant Recipients

Purpose: The impact of antigenic imprinting, when immune memory of one antigen influences the response to subsequent similar antigens, on the antibody response in solid organ transplant recipients (SOTRs) after SARS-CoV-2 vaccination is currently unknown. This study examines the relationship between seasonal coronaviruses (sCoV) and SARS-CoV-2 antibody levels pre- and post-vaccination in SOTRs. Method(s): Plasma from 52 SOTRs pre- and post-SARS-CoV-2 vaccination (2 doses, mRNA) was analyzed using the Meso Scale Diagnostic Coronavirus Panel 3 (an electrochemiluminescence detection-based multiplexed sandwich immunoassay) for IgG antibodies against alpha sCoVs (229E, NL63), beta sCoVs (HKU1, OC43), and SARS-CoV-2 spike proteins. Changes in IgG titers were determined by paired Wilcoxon rank-sum tests. Spearman correlation analysis was used to determine associations between pre-vaccination anti-sCoVs and post-vaccination anti-SARS-CoV-2 IgG. Result(s): Vaccination increased both anti-SARS-CoV-2 (fold change (FC) 1.9, p<0.001) and anti-beta sCoV (HKU1 [FC 0.05, p<0.001], OC43 [FC 0.8, p<0.001]) IgG titers in SOTRs, but did not increase anti-alpha sCoV IgG. Furthermore, prevaccination anti-beta sCoV (HKU1 [rho= -0.3, p=0.03], OC43 [rho= -0.3, p<0.03]) IgG titers were negatively correlated with post-vaccination anti-SARS-CoV-2 IgG. Conclusion(s): These exploratory findings suggest that prior exposure to seasonal betacoronaviruses may lead to antigenic imprinting in SOTRs that negatively impacts the antibody response to vaccination against the novel pandemic betacoronavirus, SARS-CoV-2.

Effect of a Fourth COVID-19 Vaccine Dose on Omicron Variant Neutralization in Solid Organ Transplant Recipients

Purpose: Humoral response to COVID-19 vaccines is attenuated in many solid organ transplant recipients (SOTRs), necessitating additional primary and booster vaccinations. The omicron variant demonstrates substantial immune evasion, and it is not known if boosters increase neutralizing capacity versus omicron among SOTRs. We therefore investigated SOTR antibody response and neutralization versus variants of concern (VOC) including omicron to a 4th vaccine dose (D4). Method(s): Within a national, prospective observational cohort, 25 SOTRs underwent anti-SARS-CoV-2 spike and receptor binding domain (RBD) IgG testing using the Meso Scale Discovery platform before and 2-4 weeks after D4. Surrogate neutralization (%ACE2 inhibition [%ACE2i], range 0-100% with >20% correlating with live virus neutralization), was measured versus full spike proteins of the ancestral ("vaccine") strain and 5 VOCs including delta and omicron. Change in IgG level and %ACE2i were compared using paired Wilcoxon rank-sum testing. Result(s): Demographics are outlined in Table 1, including median (IQR) age 59 (45- 55) years, 64% kidney recipients, and D4 receipt (60% Moderna, 40% Pfizer) median (IQR) 93 days (28-134) post D3. Two participants had SARS-CoV-2 exposure per anti-nucleocapsid testing, including one incident infection. Overall, anti-RBD (92%- >100%) and anti-spike (84%->92%) seropositivity increased after D4, as did median (IQR) anti-spike IgG 42.3 (4.9-134.2)->228.9 (115.4-655.8) WHO binding antibody units (p<0.05). Median (IQR) %ACE2i significantly increased after D4 vs the vaccine strain 5.8% (0-16.8)->20.6% (5.8-45.9) and delta variant 9.1% (4.9-12.8)->17.1% (10.3-31.7) (both p<0.001). In contrast, no SOTR showed neutralization vs omicron before or after D4: median (IQR) %ACE2i 4.1% (0-6.9)->0.5% (0-5.7) (p=0.11). Conclusion(s): Although a 4th vaccine dose increased anti-spike IgG and neutralizing capacity vs some VOC, there was no omicron variant neutralization among SOTRs. SOTRs may remain at high risk for SARS-CoV-2 infection despite boosting, thus additional protective interventions should be urgently explored. (Figure Presented).

Kinetics and Durability of a Third Dose of SARS-CoV-2 Vaccination Among Solid Organ Transplant Recipients

Purpose: Understanding the dynamics of antibody response to a third dose (D3) of anti-SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs) is important to inform booster strategies. Method(s): We studied the the dynamics of anti-RBD (Roche, <0.8 to >2500 U/dL) and anti-S (Euroimmun, 0.1 to >8.9 AU) antibody levels in a cohort of SOTRs at 2 weeks, 1 month and 3 months after D3. We compared the proportion of seroconversion at 1 month or 3 months after D3 between mRNA and Ad.26.COV2.S D3 recipients, using Poisson regression with robust standard error, adjusting for age and numbers of immunosuppressants. Result(s): Among 928 SOTRs with 2-week (n=655), 1-month (n=651) or 3-month (n=404) post-D3 titer, 78%, 82% and 86% tested positive for antibodies. The median (IQR) anti-RBD at the three timepoints were >2500 (73, >2500), 2494 (49, >2500) and 1234 (59, >2500) U/mL (Figure 1A, blue), and there were 61% (n=436), 60% (n=491) and 53% (n=313) with anti-RBD> 1000 u/mL, respectively. The median (IQR) anti-S at the three timepoints were 3.2 (0.3, 8.4), 8 (2, >8.9) and 7.4 (2, >8.9) AU (Figure 1B, blue), and there were 47% (n=218), 61% (n=161) and 64% (n=91) who developed anti-S>4 AU. Among patients with no or minimal immune response at 2 weeks post-D3 (n=102), 3/41 (7%) had increased anti-RBD by 1 month while 11/18 (61%) had increased anti-S (Fisher exact p<0.001). 6/29 (21%) had increased anti-RBD by 3 months while 12/20 (60%) had increased anti-S (p<0.01) (Figure 1A&B, yellow). 27/102 (27%) of them seroconverted at 1 or 3 months after D3. Having received Ad.26.COV2.S as D3 is associated with 3.9X increased proportion of seroconversion at 1 month or 3 months among patients with no or minimal immune response at 2 weeks after D3 (aIRR=2.223.926.92, p<0.001). Conclusion(s): Among SOTRs who received a booster anti-SARS-CoV-2 vaccination, dynamics of Anti-RBD and Anti-S antibodies differed substantially. Anti-RBD titers on average declined only slightly after 14 days post-D3, while anti-S increased up through 30-60 days post-D3. After the peak, average titer values for both antibodies declined slightly through three months post-D3.

Three Month Antibody Durability and Kinetics in SARS-CoV-2 Mrna Vaccinated Heart and Lung Transplant Recipients: Differences Above the Diaphragm

Purpose: Heart and lung transplant (HT/LT) recipients have impaired humoral responses to SARS-CoV-2 vaccination compared to other solid organ transplant recipients (SOTRs). The purpose of this study is to describe antibody titer kinetics and durability among HT and LT recipients. Method(s): HT or LT recipients (> 18 years) with no known COVID-19 infection were included. Demographics and clinical characteristics were collected via survey. Serologic testing was performed on the Roche Elecsys anti-SARS-CoV-2 enzyme immuno-assay (EIA) or the EUROIMMUN EIA pre- and post-dose 2 (D2). Result(s): Among 93 HT recipients, 59 (63%) were seropositive 1 month and 66 (71%) 3 months post-D2 (Table 1). Seropositive HT recipients had a higher median length of time from transplant to vaccination. 7/66 (11%) had delayed seroconversion (were negative for antibodies 1-month post-D2). Median(IQR) anti-RBD was 81 (8, 250) 1-month post-D2 (n=38) and 231 (48, 438) U/mL 3-months post-D2 (n=43) (Figure 1). Among 68 LT recipients, 29/68 (43%) were seropositive 1-month and 30 (44%) 3-months post-D2. Seronegative LT recipients were more likely to younger (18-39 years old, 15% vs 3%), or older (> 60 years, 74% vs. 50%, p=0.01). Seronegative LT recipients were more likely to be on anti-metabolite therapy (79% vs. 53%, p=0.04) and had a lower median length of time from transplant to vaccination. Among seropositive LT recipients at 3-months, 3 (10%) had delayed seroconversion. Median (IQR) anti-RBD was 61 (4, 233) U/mL 1-month post-D2 (n=26) and 45(11, 299) U/mL 3-months post-D2. Conclusion(s): HT and LT recipients develop a delayed and variable antibody response to mRNA SARS-CoV-2 vaccination. HT recipients more frequently seroconverted, and had higher anti-RBD levels, than LT recipients. Persistent negative and low antibody titers may place LT recipients at the highest risk of breakthrough SARSCoV- 2 infection among SOTRs.

Six-Month Antibody Kinetics and Durability After Three Doses of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

Purpose: Some solid-organ transplant recipients (SOTRs) with low or negative antibody levels after a 2-dose mRNA vaccine series against SARS-CoV-2 experience boosting after a third dose (D3), but long-term antibody durability after D3 is unknown. We describe six-month SARS-CoV-2 antibody kinetics and durability in 31 SOTRs who received D3. Method(s): 31 SOTRs without prior COVID-19 were identified within our national observational study. Serologic testing was performed a median of 30 (IQR 27-40) days after D3 and repeated at a median of 166 (148-184) days after D3. Semiquantitative anti-spike serologic testing using the Roche Elecsys anti-S enzyme immunoassay (EIA) or EUROIMMUN anti-S1 EIA was performed. Result(s): Over 6 months of follow-up, antibody levels increased in 16/27(59%), remained stable in 6/27(22%) (one negative, the others above the assay limit), and decreased in 5/27(19%). One-month post-D3, 24/31(77%) were seropositive and 7/31(23%) were seronegative. Six-months post-D3, 29/31(94%) were seropositive and 2/31(6%) remained seronegative. Both nonresponders received the BNT-162b2 primary series;one received Ad.26.CoV2.S and the other mRNA-1273 for D3. This difference in seroconversion after D3 was not statistically significant (Fisher exact = 0.49, between primary series). There were no reported cases of COVID-19 during the study period. Conclusion(s): We observed a very high rate of seroconversion after D3 in SOTRs, with marked heterogeneity in timing and strength of response depending on baseline antibody level and vaccine platform received. These results are encouraging evidence for the durable immunogenicity of additional vaccine doses in most SOTRs, and demonstrate the need for dedicated analysis of heterologous boosting strategies.

B Cells Fit for Germinal Center Activity Predict Response to a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs. Method(s): Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series. Result(s): Notably, even in the absence anti-spike antibody after two doses, spikespecific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased classswitched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells. Conclusion(s): This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation. (Figure Presented).

Effect of Mycophenolate Mofetil Dosing on Antibody Response to SARS-CoV-2 Vaccination in Heart and Lung Transplant Recipients

Purpose: Mycophenolate mofetil (MMF) use is associated with decreased antibody response to the SARS-CoV-2 mRNA vaccine series in heart and lung transplant recipients (HLTRs). Higher MMF doses have been associated with poor immunogenicity in kidney transplant recipients, but limited data exist on HLTRs. We evaluated the relationship between daily MMF dose and vaccine-induced antibody response in HLTRs. Method(s): HLTRs (n= 212) from an observational cohort were categorized by daily MMF doses (None, Low: <1000mg, Moderate: 1000-2000mg, High: >=2000mg). Semi-quantitative antibody testing was performed at 1, 3, and 6-months post-dose 2 (D2) using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA), testing for antibodies to SARSCoV2 spike protein receptor binding domain, and the EUROIMMUN EIA, testing for S1 domain of SARS-CoV-2 spike protein. Multivariable Poisson regression was used to estimate the risk of a negative antibody response with increasing MMF dose. Result(s): At the time of vaccination, 94 (44.3%) HLTRs reported receiving no MMF, 33 (15.6%) reported a low dose, 54 (25.7%) reported a moderate dose, and 31 (14.8%) reported a high dose regimen. There were statistically significant differences in the number of participants on mTOR inhibitors and Triple immunosuppression among the groups but the participants in all 4 dose categories were otherwise comparable (Table 1) The risk ratio of a negative post-D2 titer with low, moderate and high dose regimens compared to no MMF was 0.65 1.15 2.05 (p=0.63), 1.34 2.043.10 (p=0.001) and 1.83 2.77 4.21 (p<0.001) after adjusting for age, sex, vaccine type, time since transplant, and corticosteroid use. Conclusion(s): HLTRs taking MMF >1000mg/day are at higher risk of remaining seronegative after mRNA vaccination, with evidence of a dose-nonresponse effect. The findings support the exploration of whether targeted MMF reduction strategies in HLTRs increase SARS-CoV-2 vaccine immunogenicity. (Table Presented).