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Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

ABSTRACT: Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4⁺ T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs). Anti-S IgG, IgA, and IgG subclasses 1 and 3 increased after vaccination and correlated with neutralization activity in HCs and patients with oPADs. However, 42% of CVID patients developed such responses after the 2nd dose. A similar pattern was also observed with S-specific CD4⁺ T-cells as determined by OX40 and 4-1BB expression. Patients with poor anti-S IgG response had significantly lower levels of baseline IgG, IgA, CD19⁺ B-cells, switched memory B-cells, naïve CD8⁺ T-cells, and a higher frequency of EM CD8⁺ T-cells and autoimmunity compared to patients with adequate anti-S IgG responses. Patients with oPADs can develop humoral and cellular immune responses to vaccines similar to HCs. However, a subset of CVID patients exhibit impairment in developing such responses, which can be predicted by the baseline immune profile and history of autoimmunity.

SUBMITTER: Shin JJ

PROVIDER: S-EPMC9203263 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Shin Junghee Jenny JJ Par-Young Jennefer J Unlu Serhan S McNamara Andrew A Park Hong-Jai HJ Shin Min Sun MS Gee Renelle J RJ Doyle Hester H Afinogenova Yuliya Y Zidan Elena E Kwah Jason J Russo Armand A Mamula Mark M Hsu Florence Ida FI Catanzaro Jason J Racke Michael M Bucala Richard R Wilen Craig C Kang Insoo I

Journal of clinical immunology 20220617 6

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4<sup>+</sup> T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis ...[more]

PMID: 35713752

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Project description:Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg mRNA) and mRNA-1273 (100 μg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 μg mRNA) than BNT162b2 (30 μg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.

Dataset Information

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Publications

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

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