Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Ainsua-Enrich, Erola; Pedreño-López, Núria; Bracke, Carmen; Ávila‐Nieto, Carlos; Concepción, Maria Luisa Rodrı́guez de la; Pradenas, Edwards; Trinité, Benjamín; Marfil, Sílvia; Miranda, Cristina; González, Sandra; Toledo, Renata Ferraz de; Font, Marta; Benet, Susana; Escribà, Tuixent; Jiménez-Moyano, Esther; Peña, Ruth; Cedeño, Samandhy; Prado, Julia G.; Mothe, Beatriz; Berthou, Christian; Izquierdo-Useros, Núria; Vergara‐Alert, Júlia; Segalés, Joaquím; Massanella, Marta; Benitez, Rosa; Romero, Alba; Molina-Morant, Daniel; Blanco, Julià; Clotet, Bonaventura; Mateu, Lourdes; Pedro‐Botet, María Luisa; Carrillo, Jorge

doi:10.1016/j.isci.2022.105455

Cited by 11 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite detectable SARS-CoV-2 antibodies after two COVID-19 vaccinations, humoral immune response in CVID patients differed substantially from healthy individuals as SARS-CoV-2 spike antibodies in CVID patients showed a significantly reduced avidity in comparison to HC. Our study complements recently published data on avidity in CVID patients after COVID-19 vaccination [ 9 , 16 ]. In contrast to our data, Sauerwein et al observed similar levels of specific SARS-CoV-2 antibody levels and avidity in HC and CVID patients after two vaccinations, but reported lower avidity and antibodies after (3 rd ) booster vaccination [ 16 ].…”

Section: Discussionsupporting

confidence: 87%

“…Conflicting results may be due to different methodologies or might be related to the later time point of analysis and waning antibody levels. However, data from a kinetic study in CVID patients showed relatively stable anti-spike IgG antibody levels 4 weeks and 20 weeks after 2 nd COVID-19 vaccination and a positive trend for increased avidity after 3 rd vaccination [ 9 ]. Immunological and genetic heterogeneity within the group of COVID-19 seroresponding CVID patients are likely to contribute to the different observations.…”

Section: Discussionmentioning

confidence: 99%

“…While healthy control was analyzed earlier, all participating individuals were evaluated at least 4 weeks after 2 nd vaccination. Multiple studies show a stable specific SARS-CoV-2 CD4 + cellular immune response between 2 weeks and 6 months after second COVID-19 vaccination in healthy individuals [ 9 , 32 , 33 ] and for CVID patients [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Functional assessments of humoral immunity already revealed that CVID patients express lower neutralizing antibody levels than healthy individuals [ 8 – 11 , 15 ]. Avidity of generated antibodies was analyzed in two recent studies, reporting similar levels of antibody avidity in CVID patients and healthy individuals 4 weeks after second COVID-19 vaccination but without significant increase after more than two vaccinations [ 9 , 16 ]. Detailed characterizations regarding B cell memory formation are limited and suggest an atypical memory formation [ 17 ].…”

Section: Introductionmentioning

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%

See 4 more Smart Citations

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.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%