Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency

Arroyo‐Sánchez, Daniel; Cabrera-Marante, Óscar; Laguna‐Goya, Rocío; Almendro-Vázquez, Patricia; Carretero, Octavio; Gil‐Etayo, Francisco Javier; Suàrez-Fernández, Patricia; Pérez‐Romero, Pilar; Frías, Edgard Rodríguez de; Serrano, Antonio; Allende, Luís M.; Pleguezuelo, Daniel; Paz‐Artal, Estela

doi:10.1007/s10875-021-01174-5

Cited by 52 publications

(61 citation statements)

References 34 publications

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“…As shown previously for XLA and CVID patients after vaccination against seasonal influenza or hepatitis B (53-55), induction of specific T cell immunity is also detectable after COVID-19 vaccination in IEI patients (25)(26)(27)(28).…”

Section: Discussionsupporting

confidence: 77%

“…(Cross) reactive T cells against other endemic human coronaviruses were found in CVID patients (23), and a group of five mild COVID-19 cases in PAD patients, with largely preserved specific antibody response, was recently reported to generate a robust T cell response (24). In addition, studies in PAD patients reported detectable specific T cell responses after COVID-19 vaccination (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

et al. 2022

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Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

et al. 2022

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“…Spike-specific T-cells responses were induced in CVID patients with a variable frequency ( 37 , 38 ), differently from T cells produced after multiple exposures to influenza viral antigen following immunization or infection. In a recent study, the vast majority of CVID patients had S1-specific T cells compared after two doses of immunization with mRNA vaccine ( 39 ). In our study ( 27 ), differently from influenza immunization, poor Spike-specific T-cell responses were generated by immunization.…”

Section: Insight On Sars-cov-2mentioning

confidence: 99%

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

2022

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CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses to a novel antigen. In CVID, as in immunocompetent subjects, the role of B and T cells is different between infected and vaccinated individuals. Upon vaccination, variable anti-Spike IgG responses have been found in different CVID cohorts. Immunization with two doses of mRNA vaccine did not generate Spike-specific classical memory B cells (MBCs) but atypical memory B cells (ATM) with low binding capacity to Spike protein. Spike-specific T-cells responses were also induced in CVID patients with a variable frequency, differently from specific T cells produced after multiple exposures to viral antigens following influenza virus immunization and infection. The immune response elicited by SARS-CoV-2 infection was enhanced by subsequent immunization underlying the need to immunize convalescent COVID-19 CVID patients after recovery. In particular, immunization after SARS-Cov-2 infection generated Spike-specific classical memory B cells (MBCs) with low binding capacity to Spike protein and Spike-specific antibodies in a high percentage of CVID patients. The search for a strategy to elicit an adequate immune response post-vaccination in CVID patients is necessary. Since reinfection with SARS-CoV-2 has been documented, at present SARS-CoV-2 positive CVID patients might benefit from new preventing strategy based on administration of anti-SARS-CoV-2 monoclonal antibodies.

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“…Patients were considered SARS-CoV-2 seropositive if antibody titers determined by ELISA were higher than 50 (limit of detection of the assay) and they were considered to have positive neutralizing antibodies if the titer was greater than 3.3 ( 36 ). Results were expressed as the mean ± standard deviation (SD) for continuous variables with parametric distribution or the median with interquartile range (IQR) for those with non-parametric distribution.…”

Section: Methodsmentioning

confidence: 99%

Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients

et al. 2022

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IntroductionThere is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients.MethodsA prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed.ResultsPatients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors (p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection (p< 0.001), and than patients who required oxygen therapy (p< 0.05), and had 5-fold higher IgG1 titers than RF non-survivors (p< 0.001) and those who needed oxygen therapy (p< 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission (p< 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived (p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036).ConclusionsWe demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection.

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Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency

Cited by 52 publications

References 34 publications

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients

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