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Immunity to SARS-CoV-2: Humoral and Cellular Immune Response

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 8906

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Special Issue Editor

Dr. Cinzia Giagulli

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Guest Editor

Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: host/pathogens interactions; intracellular pathogens; new therapeutic treatments

Special Issue Information

Dear Colleagues,

In the effort to control SARS-CoV-2 transmission and COVID-19, public health agencies are globally aimed to increase population immunity by vaccination. The introduction of highly effective vaccines provided a current intervention to reduce the risk and severity of SARS-CoV-2 infection.

Immunity through vaccination or acquired following natural infection are the two means to build up population immunity. The assessment of immune responses induced by vaccination has largely focused on the development of antibodies targeting the S1 domain of the SARS-CoV-2 spike protein. The key benefit of vaccine regimens is that the anti-S IgG titer is higher than for natural infection one, but seroprevalence cannot always necessarily be assumed as a protection marker.

However, both SARS-CoV-2 vaccination and natural infection induce specific antibodies with neutralizing activity, but the duration of such humoral protection is unclear since antibody-levels wane over time. On the other side, recent several findings have underlined an effective and robust long-term T-cell mediated responses to SARS-CoV-2 infection in COVID-19 vaccinated or in previously infected individuals. Indeed, the adaptive immune responses play critical roles in viral clearance and protection against re-infection.

Additionally, limited studies have assessed the effect of pharmacological treatments on humoral and T cell immune responses to COVID-19 vaccination in people affected by different diseases. Finally, the emergence of SARS-CoV-2 variants of concern (VOC), that have acquired mutations in S protein with consequent increased transmissibility, severity and immune escape potential, also underscore the need for additional studies and a continuous characterization of emerging variants beside the durability of antibody and T cell responses to viral variants.

Thus, in this Special Issue, we aim to explore both humoral and T cell responses to vaccination and people undergoing various pharmacological treatments, and the mechanisms behind them.

Dr. Cinzia Giagulli
Guest Editor

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Keywords

adaptive immunity against SARS-CoV-2
T cell immunity to SARS-CoV-2
humoral and cellular immune response
antibody

Published Papers (5 papers)

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Research

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11 pages, 1812 KiB

Open AccessArticle

Animals Experimentally Infected with SARS-CoV-2 Generate Functional Autoantibodies against G-Protein-Coupled Receptors

by Gerd Wallukat, Kerstin Wernike, Dipthi Bachamanda Somesh, Thomas C. Mettenleiter and Johannes Müller

Biomedicines 2023, 11(10), 2668; https://doi.org/10.3390/biomedicines11102668 - 28 Sep 2023

Cited by 3 | Viewed by 785

Abstract

(1) Background: SARS-CoV-2 infection has been linked to diverse clinical manifestations in humans, including cardiovascular complications. Functional autoantibodies targeting G-protein-coupled receptors have emerged as potential contributors to these effects. This study sought to investigate the production and activity of functional autoantibodies targeting G-protein-coupled receptors after SARS-CoV-2 infection of selected animal species. (2) Methods: The presence of functional autoantibodies such as 2-adrenoceptor, angiotensin II AT1 receptor, muscarinic M2 receptor, and angiotensin 1–7 MAS receptor was assessed in cattle and ferrets experimentally infected with SARS-CoV-2. Bioassays were conducted to evaluate the positive or negative chronotropic responses induced by these autoantibodies. Further experiments identified the extracellular domains to which the functional autoantibodies bind, and receptor antagonists were employed to block the induced responses. (3) Results: Only two out of six cattle that were inoculated with SARS-CoV-2 displayed viral replication and tested positive for functional autoantibodies against G-protein-coupled receptors. These functional autoantibodies specifically recognized β2-adrenoceptor, angiotensin II AT1 receptor, muscarinic M2 receptor, and angiotensin 1–7 MAS receptor and induced distinct positive and negative chronotropic effects in the bioassay. Infected ferrets generated functional autoantibodies against β2-adrenoceptor and muscarinic M2 receptor and presented bioactivity similar to that in cattle. (4) Conclusions: This study uncovers functional autoantibodies targeting G-protein-coupled receptors in cattle and ferrets post-SARS-CoV-2 infection, with implications for cardiovascular function. Full article

(This article belongs to the Special Issue Immunity to SARS-CoV-2: Humoral and Cellular Immune Response)

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14 pages, 1164 KiB

Open AccessArticle

Specific Cellular and Humoral Response after the Third Dose of Anti-SARS-CoV-2 RNA Vaccine in Patients with Immune-Mediated Rheumatic Diseases on Immunosuppressive Therapy

by Kauzar Mohamed Mohamed, María Paula Álvarez-Hernández, Carlos Jiménez García, Kissy Guevara-Hoyer, Dalifer Freites, Cristina Martínez Prada, Inés Pérez-Sancristóbal, Benjamín Fernández Gutiérrez, Gloria Mato Chaín, Maria Rodero, Antonia Rodríguez de la Peña, Teresa Mulero, Cecilia Bravo, Esther Toledano, Esther Culebras López, Beatriz Mediero Valeros, Pedro Pérez Segura, Silvia Sánchez-Ramón and Gloria Candelas Rodríguez

Biomedicines 2023, 11(9), 2418; https://doi.org/10.3390/biomedicines11092418 - 29 Aug 2023

Viewed by 1117

Abstract

Objective: Data on cellular and humoral immunogenicity after the third dose of anti-SARS-CoV-2 vaccines in patients with immune-mediated rheumatic diseases (IMRDs) are scarce. Herein, we evaluated the adaptive immune response in IMRD patients treated with different immunosuppressive therapies (conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biological disease-modifying antirheumatic drugs [bDMARDs], and targeted synthetic disease-modifying antirheumatic drugs [tsDMARDs]) after the booster of the anti-SARS-CoV-2 vaccine to determine whether any drug reduced the vaccine’s response. Methods: A single-center prospective study was conducted, including patients presenting with IMRD and healthy controls (HC). Specific anti-SARS-CoV-2 interferon-gamma (IFN-γ) production was evaluated between 8–12 weeks after the third dose of the SARS-CoV-2 vaccine. In addition, anti-Spike IgG antibody titers were also measured. Results: Samples were obtained from 79 IMRD patients (51 women, 28 men; mean age 57 ± 11.3 years old): 43 rheumatoid arthritis, 10 psoriatic arthritis, 14 ankylosing spondylitis, 10 undifferentiated spondyloarthritis, and 2 inflammatory bowel disease-associated spondyloarthritis (IBD-SpA). In total, 31 HC (mean age 50.9 ± 13.1 years old, 67.7% women) were included in the study. Post-vaccine results displayed positive T-cell immune responses in 68 out of 79 (86.1%) IMRD patients (82.3% of those without prior COVID-19). All HC and IMRDs patients had an antibody response against the SARS-CoV-2 receptor-binding domain; however, the HC response was significantly higher (median of 18,048 AU/mL) than in IMRDs patients (median of 6590.3 AU/mL, p < 0.001). MTX and leflunomide were associated with lower titers of IgG and IFN-γ responses. Among bDMARDs, adalimumab, etanercept, and guselkumab are associated with reduced cellular responses. Conclusion: Our preliminary data show that the majority of our IMRD patients develop cellular and humoral responses after the SARS-CoV-2 booster vaccination, emphasizing the relevance of vaccination in this group. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. Specific vaccination protocols and personalized decisions about boosters are essential for these patients. Full article

(This article belongs to the Special Issue Immunity to SARS-CoV-2: Humoral and Cellular Immune Response)

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11 pages, 946 KiB

Open AccessArticle

Immunogenicity of BNT162b2 mRNA-Based Vaccine against SARS-CoV-2 in People with Cystic Fibrosis According to Disease Characteristics and Maintenance Therapies

by Gianfranco Alicandro, Valeria Daccò, Lisa Cariani, Chiara Rosazza, Calogero Sathya Sciarrabba, Federica Ferraro, Chiara Lanfranchi, Paola Medino, Daniela Girelli and Carla Colombo

Biomedicines 2022, 10(8), 1998; https://doi.org/10.3390/biomedicines10081998 - 17 Aug 2022

Cited by 3 | Viewed by 1522

Abstract

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on the immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged > 12 and who were followed-up in our CF center and received two doses of the BNT162b2 vaccine in the period of March–October 2021. Blood samples were taken from them for the quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and 3 and 6 months after the second dose. We enrolled 143 patients (median age: 21 years, range: 13–38), 16 of whom had had a previous infection. Geometric mean antibody titer (GMT) 3 months after vaccination was 1355 U/mL (95% CI: 1165–1575) and decreased to 954 U/mL (95% CI: 819–1111) after 6 months (p < 0.0001). GMT was higher among previously infected patients as compared to those naïve to SARS-CoV-2 (6707 vs. 1119 U/mL at 3 months and 4299 vs. 796 U/mL at 6 months, p < 0.0001) with no significant differences in the rate of decline over time (p = 0.135). All pwCF mounted an antibody response after two doses of the BNT162b2 vaccine, which waned at 6 months from vaccination. Age ≥ 30 years and the use of inhaled corticosteroids were associated with a lower humoral response. Between the second and the third doses, nine episodes of vaccine breakthrough infections were observed. Full article

(This article belongs to the Special Issue Immunity to SARS-CoV-2: Humoral and Cellular Immune Response)

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17 pages, 2195 KiB

Open AccessArticle

Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines

by Sergio Gil-Manso, Diego Carbonell, Verónica Astrid Pérez-Fernández, Rocío López-Esteban, Roberto Alonso, Patricia Muñoz, Jordi Ochando, Ignacio Sánchez-Arcilla, Jose M Bellón, Rafael Correa-Rocha and Marjorie Pion

Biomedicines 2022, 10(7), 1676; https://doi.org/10.3390/biomedicines10071676 - 12 Jul 2022

Cited by 5 | Viewed by 2169

Abstract

Vaccination against SARS-CoV-2 has become the main method of reducing mortality and severity of COVID-19. This work aims to study the evolution of the cellular and humoral responses conferred by two mRNA vaccines after two doses against SARS-CoV-2. On days 30 and 240 after the second dose of both vaccines, the anti-S antibodies in plasma were evaluated from 82 volunteers vaccinated with BNT162b2 and 68 vaccinated with mRNA-1273. Peripheral blood was stimulated with peptides encompassing the entire SARS-CoV-2 Spike sequence. IgG Anti-S antibodies (humoral) were quantified on plasma, and inflammatory cytokines (cellular) were measured after stimulation. We observed a higher response (both humoral and cellular) with the mRNA-1273 vaccine. Stratifying by age and gender, differences between vaccines were observed, especially in women under 48 and men over 48 years old. Therefore, this work could help to set up a vaccination strategy that could be applied to confer maximum immunity. Full article

(This article belongs to the Special Issue Immunity to SARS-CoV-2: Humoral and Cellular Immune Response)

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Review

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20 pages, 1380 KiB

Open AccessReview

Hybrid Immunity to SARS-CoV-2 from Infection and Vaccination—Evidence Synthesis and Implications for New COVID-19 Vaccines

by Julia R. Spinardi and Amit Srivastava

Biomedicines 2023, 11(2), 370; https://doi.org/10.3390/biomedicines11020370 - 27 Jan 2023

Cited by 16 | Viewed by 2577

Abstract

COVID-19 has taken a severe toll on the global population through infections, hospitalizations, and deaths. Elucidating SARS-CoV-2 infection-derived immunity has led to the development of multiple effective COVID-19 vaccines and their implementation into mass-vaccination programs worldwide. After ~3 years, a substantial proportion of the human population possesses immunity from infection and/or vaccination. With waning immune protection over time against emerging SARS-CoV-2 variants, it is essential to understand the duration of protection, breadth of coverage, and effects on reinfection. This targeted review summarizes available research literature on SARS-CoV-2 infection-derived, vaccination-elicited, and hybrid immunity. Infection-derived immunity has shown 93–100% protection against severe COVID-19 outcomes for up to 8 months, but reinfection is observed with some virus variants. Vaccination elicits high levels of neutralizing antibodies and a breadth of CD4+ and CD8+ T-cell responses. Hybrid immunity enables strong, broad responses, with high-quality memory B cells generated at 5- to 10-fold higher levels, versus infection or vaccination alone and protection against symptomatic disease lasting for 6–8 months. SARS-CoV-2 evolution into more transmissible and immunologically divergent variants has necessitated the updating of COVID-19 vaccines. To ensure continued protection against SARS-CoV-2 variants, regulators and vaccine technical committees recommend variant-specific or bivalent vaccines. Full article

(This article belongs to the Special Issue Immunity to SARS-CoV-2: Humoral and Cellular Immune Response)

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