Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency

Nielsen, Bent; Drabe, Camilla Heldbjerg; Barnkob, Mike Bogetofte; Johansen, Işik Somuncu; Hansen, Anne Kirstine Kronborg; Nilsson, Anna Christine; Rasmussen, Line Dahlerup

doi:10.3389/fimmu.2022.934476

Cited by 14 publications

(29 citation statements)

References 25 publications

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“…Limitations of our study include the slight heterogeneity of administered COVID-19 vaccines and that interpretation is restricted to patients after receiving two COVID-19 vaccinations. While more than two vaccinations were shown to increase humoral immune response in CVID patients (31), it remains uncertain whether repeated vaccinations could also translate into B cell memory formation. Due to increased levels of SARS-CoV-2-IgG antibodies in commercially available immunoglobulins (32), a mere serological evaluation does no longer allow to distinguish between passive immunization and active antibody generation.…”

Section: Discussionmentioning

confidence: 99%

Impaired B cell recall memory and reduced antibody avidity but robust T cell response in CVID patients after COVID-19 vaccination

Steiner¹,

Schwarz²,

Corman³

et al. 2023

Preprint

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Purpose: Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2 specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients. Methods: We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pTFH) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine. Results: SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. 100% of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen specific CD4+CD154+CD137+CXCR5+ pTFH cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pTFH did not correlate with antibody response or avidity. Conclusion: Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired B cell recall memory and reduced antibody avidity but robust T cell response in CVID patients after COVID-19 vaccination

Steiner¹,

Schwarz²,

Corman³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Limitations of our study include the slight heterogeneity and timing of administered COVID-19 vaccines and that interpretation is restricted to patients after receiving two COVID-19 vaccinations. While more than two vaccinations were shown to increase humoral immune response in CVID patients [ 18 ], it remains uncertain whether repeated vaccinations could also translate into B cell memory formation. Due to increased levels of SARS-CoV-2-IgG antibodies in commercially available immunoglobulins [ 45 ], a mere serological evaluation does no longer allow to distinguish between passive immunization and active antibody generation.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed characterizations regarding B cell memory formation are limited and suggest an atypical memory formation [ 17 ]. Without affecting seroconversion rates, booster vaccination in CVID patients was shown to further increase antibody levels in some seroresponder [ 9 , 18 ], while effects of boosting on specific T cell immunity is variable [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Impaired B Cell Recall Memory and Reduced Antibody Avidity but Robust T Cell Response in CVID Patients After COVID-19 Vaccination

et al. 2023

View full text Add to dashboard Cite

Purpose Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2-specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients. Methods We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pTFH) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine. Results SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. One hundred percent of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen-specific CD4+CD154+CD137+CXCR5+ pTFH cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pTFH did not correlate with antibody response or avidity. Conclusion Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.

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“…Despite the recent introduction of new bivalent vaccine formulations (6), a large proportion of immunocompromised patients received the fourth dose with the monovalent vaccine carrying the wild type mRNA. However, in some conditions, such as common variable immunodeficiency (CVID), while the third dose definitely improved their antibody titers, a fourth dose was only slightly improving the response (7). If the study included a higher number of patients (currently n=33) there could have been a statistically significant improvement of the response.…”

Section: Introductionmentioning

confidence: 99%

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

Rescigno

Agrati²,

Salvarani³

et al. 2023

Front. Immunol.

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IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

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Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency

Cited by 14 publications

References 25 publications

Impaired B cell recall memory and reduced antibody avidity but robust T cell response in CVID patients after COVID-19 vaccination

Impaired B cell recall memory and reduced antibody avidity but robust T cell response in CVID patients after COVID-19 vaccination

Impaired B Cell Recall Memory and Reduced Antibody Avidity but Robust T Cell Response in CVID Patients After COVID-19 Vaccination

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

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