Vaccination in PADs

Milito, Cinzia; Soccodato, Valentina; Collalti, Giulia; Lanciarotta, Alison; Bertozzi, Ilaria; Rattazzi, Marcello; Scarpa, Riccardo; Cinetto, Francesco

doi:10.3390/vaccines9060626

Cited by 12 publications

(12 citation statements)

References 33 publications

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“…As stated above, immunization can be used in patients with impaired and residual B-cell function to provide information on specific humoral immunity and to improve the outcomes related to vaccine-preventable disease. In CVID patients, vaccination is a tool to evaluate T-dependent and T-independent antibody residual function of B lymphocytes and it might be used to measure specific cellular immunity ( 15 ). Thus, vaccination has both a therapeutic and diagnostic role, but might be also useful to predict the prognosis ( 16 ).…”

Section: Vaccinations In Cvidmentioning

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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Section: Vaccinations In Cvidmentioning

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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“…After two doses of Covid-19 vaccine, decreased immune responses are expected in the elderly and in subjects under dialysis, with central obesity, arterial hypertension, smoking, transplanted patients and patients under immunosuppressive drugs, especially anti-CD20 therapies [ 6 – 11 ]. It is known that vaccination response is reduced in CVID patients [ 12 ]. For example, influenza vaccination of individuals with a hypogammaglobulinemia only resulted in significant increase of IgG antibody-titers in 29% [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease

et al. 2022

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Objectives Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. Methods This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. Results After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0–125.0), baseline IgG 3–5 g/l: 99.9 AU/ml (95%CI 14.4–400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0–400.0), healthy controls 250.0 AU/ml (95%CI 209.0–358.0), p = 0.007. Conclusion In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.

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“…While vaccination has been the central strategy in preventing or dampening the viral pandemic [49], vaccination is clearly less effective in certain circumstances exacerbated by the emergence of new SARS-CoV-2 variants which may limit or shorten the impact of certain vaccine therapies [50][51][52]. In addition, there remains an important sub-set of individuals, typically with compromized immune systems, that respond less well to vaccines [53][54][55], thus necessitating the development of additional antiviral strategies. In those regions of the world claiming a level of pandemic-control, a new and growing epidemic of patients suffering from longer-term post-infection complications, often referred to by the catch-all "long-COVID", is being increasingly reported.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein

Tan

Patton

Munro

et al. 2021

Viruses

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ORF3a has been identified as a viroporin of SARS-CoV-2 and is known to be involved in various pathophysiological activities including disturbance of cellular calcium homeostasis, inflammasome activation, apoptosis induction and disruption of autophagy. ORF3a-targeting antibodies may specifically and favorably modulate these viroporin-dependent pathological activities. However, suitable viroporin-targeting antibodies are difficult to generate because of the well-recognized technical challenge associated with isolating antibodies to complex transmembrane proteins. Here we exploited a naïve human single chain antibody phage display library, to isolate binders against carefully chosen ORF3a recombinant epitopes located towards the extracellular N terminal and cytosolic C terminal domains of the protein using peptide antigens. These binders were subjected to further characterization using enzyme-linked immunosorbent assays and surface plasmon resonance analysis to assess their binding affinities to the target epitopes. Binding to full-length ORF3a protein was evaluated by western blot and fluorescent microscopy using ORF3a transfected cells and SARS-CoV-2 infected cells. Co-localization analysis was also performed to evaluate the “pairing potential” of the selected binders as possible alternative diagnostic or prognostic biomarkers for COVID-19 infections. Both ORF3a N and C termini, epitope-specific monoclonal antibodies were identified in our study. Whilst the linear nature of peptides might not always represent their native conformations in the context of full protein, with carefully designed selection protocols, we have been successful in isolating anti-ORF3a binders capable of recognising regions of the transmembrane protein that are exposed either on the “inside” or “outside” of the infected cell. Their therapeutic potential will be discussed.

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Vaccination in PADs

Cited by 12 publications

References 33 publications

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

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

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease

Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein

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