TY - JOUR
T1 - Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy
AU - Katz Sand, Ilana
AU - Gnjatic, Sacha
AU - Krammer, Florian
AU - Tuballes, Kevin
AU - Carreño, Juan Manuel
AU - Satyanarayan, Sammita
AU - Filomena, Susan
AU - Staker, Erin
AU - Tcheou, Johnstone
AU - Miller, Aaron
AU - Fabian, Michelle
AU - Safi, Neha
AU - Nichols, Jamie
AU - Patel, Jasmin
AU - Krieger, Stephen
AU - Tankou, Stephanie
AU - Horng, Sam
AU - Klineova, Sylvia
AU - Beck, Erin
AU - Merad, Miriam
AU - Lublin, Fred
N1 - Publisher Copyright:
© 2022
PY - 2023/2
Y1 - 2023/2
N2 - Background: People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. The objective of this study is to evaluate humoral and cellular immune responses to a third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays. Methods: This is an observational study evaluating immunological responses to third COVID-19 vaccine dose in participants treated with anti-CD20 agents, S1PR modulators, and healthy controls. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Groups were compared by one-way ANOVA with Tukey multiple comparisons. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Pre-post comparisons were made by Wilcoxon paired t-tests, inter-cohort comparisons by Mann-Whitney t-test. Results: This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P < 0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p < 0.001) and were not significantly “boosted” by a third injection. Conclusions: Participants on anti-CD20 and S1PR modulator therapies had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies, but were nearly abrogated by S1PR modulators. These results have clinical implications warranting further study.
AB - Background: People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. The objective of this study is to evaluate humoral and cellular immune responses to a third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays. Methods: This is an observational study evaluating immunological responses to third COVID-19 vaccine dose in participants treated with anti-CD20 agents, S1PR modulators, and healthy controls. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Groups were compared by one-way ANOVA with Tukey multiple comparisons. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Pre-post comparisons were made by Wilcoxon paired t-tests, inter-cohort comparisons by Mann-Whitney t-test. Results: This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P < 0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p < 0.001) and were not significantly “boosted” by a third injection. Conclusions: Participants on anti-CD20 and S1PR modulator therapies had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies, but were nearly abrogated by S1PR modulators. These results have clinical implications warranting further study.
KW - Booster
KW - Covid-19
KW - Multiple sclerosis
KW - SARS-CoV-2
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85145989315&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2022.104486
DO - 10.1016/j.msard.2022.104486
M3 - Article
AN - SCOPUS:85145989315
SN - 2211-0348
VL - 70
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
M1 - 104486
ER -