ABSTRACT
Background: Patients on OCR have attenuated antibody, but largely intact T-cell responses to COVID-19 vaccination. Little is known about durability of post-vaccine responses in OCR-treated patients. Objective(s): To examine antibody and cellular responses to mRNA COVID-19 vaccines (Pfizer, BioNTech/Moderna) in Ocrelizumab (OCR)-treated MS patients over 24-week period. Method(s): MS patients on OCR were recruited from NYU (New York City) and Rocky Mountain at CU (Denver) MS Centers. Antibody responses to SARS-CoV-2 spike proteins were assessed with multiplex bead-based (MBI) immunoassays, and cellular responses to SARS-CoV-2 Spike protein with ELISpot and activation induced marker (AIM) panel in a Cytek Aurora full-spectrum flow cytometry platform. Data on samples collected pre-vaccine and 4-, 12-, 24-weeks post 2-doses and 4-, 12-weeks post-third dose will be presented. Result(s): 40/61 enrollees (age 38.3+/-10.9;77.5% female;57.5% non-white) had 24-week post-vaccination data and 9 patients had 4-week post 3rd dose data. Antibody response increased from prevaccine level of 972.0 U/mL to 6307.4 U/mL at week-4 (p=0.0002), then decreased to 4633.8 u/mL at week-12 (26% decrease from week-4, p=0.1377), and further to 2878.4 u/mL at week-24 (37% decrease from week-12, p value=0.109). Spikespecific IFNgamma T-cell responses by ELIspot were 125.7 SFU/106 cells pre-vaccine, increased to 362.9 SFU/106 cells at week-4 (p=0.009), then to 511.5 SFU/106 cells at week-12 (40.9% increase relative to 4-week time-point, p=0.8474), and remained elevated at 501.7 SFU/106 cells at week-24 (p=0.7393, 1.9% compared to week 12). 4-week post 3rd dose, Ab level increased to 5094.8 U/mL (189.9% compared to pre-3rd dose, p =0.076) and IFNgamma responses to 1253.3 SFU/106 cells (484.5% increase, p=0.037). Conclusion(s): Antibody responses to 2-series vaccine peaked at 4 weeks and trended downward thereafter, while cellular responses were sustained at 24 weeks. Third-dose resulted in marked increases in both antibody and T-cell responses 4-weeks. Expanded analyses, including in-depth immunophenotyping and 12-week post 3rd vaccination responses will be presented.
ABSTRACT
Objective: To compare humoral and cellular responses to COVID-19 vaccines in 400 consecutive MS patients who were on Ocrelizumab ('OCR') and other disease-modifying therapies ('nonOCR') at the time of vaccination. Background: Peripheral B-cell depletion with anti-CD20 therapies, attenuates humoral responses to vaccines, but less is known about cellular responses. Design/Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiepitope bead-based immunoassays (MBI) of antibody-responses to SARS-COV-2 spike proteins (threshold of 'positivity'was chosen as 2 SD below non-OCR mean);T-cell responses to SARSCoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;live virus immunofluorescence-based microneutralization assay. Results: Antibody and T cell data was available on 145/355 patients enrolled to date (mean age: 40.0 years;75% female;48% non-white;39% on OCR;12% with prior COVID-19 infection;vaccines: 58% Pfizer/BioNTech, 36% Moderna and 6% Johnson&Johnson;median vaccine-tosample time: 93 (+/-32) days). In OCR, Elecsys Anti-SARS-CoV-2 Ab titers were detected in 30/63 (48%;mean antibody titer in log scale: 1.63) and in non-OCR - in 78/81 (96%, mean Ab titer in log scale: 2.83;p<0.0001). In OCR, antibody response by MBI were detected in 41/57 (72%, mean level in log scale: 3.09) and in non OCR - in 68/72 (94%, mean level in log scale: 4.08;p<0.001). Neutralizing antibodies were detected in 10/42 (38%) of OCR and 24/43 (56%) of non-OCR (p=0.1). T-cell activation based on induced IFNg secretion (TruCulture) was observed in 50/64 (78%) OCR and 43/81 (53%) non-OCR (p=0.002). Conclusions: Preliminary results suggest robust vaccine-specific T-cell immune response to SARS-CoV2 vaccines in B-cell depleted patients, but markedly attenuated antibody responses. Final results of pre-planned multivariable analyses stratified by DMT class and high-dimensional immunophenotyping will be presented.
ABSTRACT
The COVID-19 pandemic created an unprecedented shortage of personal protective equipment (PPE) for healthcare workers-especially respirators. In response to a lack of commercial respirator equipment, a multidisciplinary prototyping hackathon was held and the key components required to develop an inexpensive, scalable "COVID-19 reusable elastomeric respirator" (RER-19) were identified. Available hospital supplies were assessed based on their published technical specifications to meet each of the key component requirements. The fully assembled prototype was then validated through user testing, and volunteers underwent standard fit testing with cardiopulmonary monitoring while wearing the RER-19 in a small pilot study. Multiple social media platforms were then used to disseminate educational information on respirator assembly, use, and maintenance. Here, we present our institution's initial experience with prototyping to meet a specific healthcare challenge, in combination with prompt dissemination of information to educate and empower healthcare workers in the face of a critical PPE shortage during an unprecedented and evolving pandemic.
ABSTRACT
Objective: To examine antibody and T-cell responses to mRNAplatform COVID-19 vaccines in Ocrelizumab-treated MS patients over a 12-month period. Introduction: B-cell depletion with Ocrelizumab attenuates humoral responses to vaccines. The kinetics of humoral and cellular immune responses to COVID-19 vaccines in B-cell depleted MS patients has not been reported. Methods: VIOLA (NCT04843774) is an open-label, observational study enrolling 60 MS patients on Ocrelizumab from NYU and Rocky Mountain at the University of Colorado MS Centers. First vaccine dose occurred ≥2 weeks after ocrelizumab infusion;second-dose ≥8 weeks before the next infusion. Antibody responses to SARS-COV-2 spike proteins were assessed with Elecsys Anti-SARS-CoV-2 (Roche Diagnostics) and multiplex bead-based immunoassays. T-cell responses to SARS-CoV-2 Spike protein were assessed with IFNγ ELISpot (Invitrogen) and TruCulture (Myriad RBM) and high-dimensional immunophenotyping. Samples are collected pre-vaccination and at 4, 12, 24, and 48-weeks post-vaccination. Results: As of 7/15/2021, 52 subjects have been enrolled (39.7±10.0 years;73% female;47% non-white), of whom 47 were fully vaccinated (85% Pfizer, 15% Moderna). Anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) were available for pre- and post-vaccine timepoints for 15 patients. Pre-vaccine, 1/15 (7%) patients had detectable titers, while at 4-weeks postvaccine, 10/15 (66%) patients had detectible titers (mean for positives: 1189 U/ml;5 patients had positive titers <25 U/ml). T-cell activation based on induced IFNγ secretion (TruCulture) at baseline and 4-week post-vaccine timepoints were available for 13 patients, of whom 12 (92%) were increased (mean pre-vaccine: 24 pg/ml;mean post-vaccine: 366 pg/ml, two-tailed t-test, p=0.0032). Conclusions: This prospective study of humoral and cellular immune responses to COVID-19 vaccines in Ocrelizumab-treated patients will generate data to help guide management of MS patients on anti-CD20 therapies. Early results suggest that 4-weeks post-vaccination nearly all Ocrelizumab-treated MS patients develop T-cell immunity and two-thirds showed evidence of humoral response. Additional 4-week and 12-week post-vaccination data will be presented.
ABSTRACT
Objective: To compare humoral and T-cell responses to COVID- 19 vaccines in 400 MS patients who were on Ocrelizumab ('OCR') v. other disease-modifying therapies ('non-OCR') at the time of vaccination. Introduction: Peripheral B-cell depletion with anti-CD20 therapies attenuates humoral responses to vaccines. Whether immune responses to COVID-19 vaccines differ between B-cell depleted and non-B cell depleted MS patients is not known. Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiplex bead-based immunoassays of antibody-responses to SARS-COV-2 spike proteins;T-cell responses to SARS-CoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;and live virus immunofluorescencebased microneutralization assay. Results: As of 7/15/2021, 105 MS subjects were enrolled (mean age: 40.5 years;76% female;41% non-white;38% on OCR;12% with prior COVID-19 infection). 95% were fully vaccinated with mRNA vaccines (Pfizer/Moderna);5% - with adenovirus-based vaccine (Johnson&Johnson). Median time from sample collection to last vaccine was 79 days. Positive Elecsys Anti-SARS-CoV-2 Ab titers post-vaccine were detected in 11/37 (30%) in OCR (mean level: 702 U/mL among seropositives) and 54/54 (100%) patients in non-OCR (mean level: 2310 U/mL;p<0.0001). Positive response by multiplex assay (threshold of 'positive' defined as 2 SD below the mean for the non-OCR) were detected in 10/27 (37%) OCR and 29/31 (94%) non-OCR (p<0.00001). T-cell activation based on induced IFNγ secretion (TruCulture) was detected in 20/25 (80%) OCR and 16/19 (84%) non-OCR patients (p=0.71). Conclusions: Preliminary results suggest robust T-cell immune response to SARS-CoV2 vaccines in approximately 80% of both OCR and non-OCR MS patients. Antibody responses were markedly attenuated in OCR compared to non-OCR group. Updated results will be presented.