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Immune Response of SARS-CoV-2 Infection

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 28759

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Special Issue Editor

Dr. Velmurugan Balaraman

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Guest Editor

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Interests: emerging zoonotic viruses; virus-vector-host interactions; recombinant vaccines; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue combines original research and review articles that focus on the immune response to SARS-CoV-2 infection, including innate and adaptive immune mechanisms that can induce protection or pathology to the host; immune response to vaccination or natural infection; host–virus interactions, including immunopathogenesis or immune evasion of the virus; and the evaluation and efficacy of vaccines and immunotherapies.

During the third year of the development of the SARS-CoV-2 pandemic, we have learned to accept novel routines and behaviors, and to appreciate the importance of high quality scientific research and effective communication. In addition to understanding the virus that causes this disease, an equally important factor to consider is the immune response induced by SARS-CoV-2 infection. From an asymptomatic to acute severe respiratory syndrome, including a vast range of potentially chronic symptoms, the manner by which the host recognizes and responds to infection must be understood to guide the treatment strategies to achieve the best possible outcome. Innate immune responses may potentially control viral replication with little systemic changes, or induce a cytokine storm that causes severe immunopathology. Adaptive immune responses induced by vaccination or natural infection should be well-defined to determine the limits of reliable and long-term protection.

This Special Issue aims to provide an in-depth knowledge of host immune responses to SARS-CoV-2 infection. The present Special Issue invites submissions of original research articles and reviews. The areas of research areas may include (but are not limited to) the following: immune response to COVID-19 natural infection versus mRNA vaccines, immune response to COVID-19 variants in vaccinated and unvaccinated people, immune response to COVID-19 infection in people with underlying conditions, the cause of vanning immunity in vaccinated people, immune response to COVID-19 in humans and animals, immune response in humans superinfected different variants.

We look forward to receiving your contributions.

Dr. Velmurugan Balaraman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

mucosal immunity
immune evasion
herd immunity
co-infections
recombinant vaccine
mRNA vaccines

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

4 pages, 192 KiB

Open AccessEditorial

From Co-Administration to Co-Formulation: The Race for New Vaccines against COVID-19 and Other Respiratory Viruses

by Daniele Focosi

Vaccines 2023, 11(1), 109; https://doi.org/10.3390/vaccines11010109 - 2 Jan 2023

Cited by 10 | Viewed by 3303

Abstract

Combined (concomitant or synchronous) vaccination is crucial to increasing the compliance rate during mass campaigns by reducing the time to deployment (i [...] Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

Research

Jump to: Editorial, Review

14 pages, 1088 KiB

Open AccessArticle

Patients’ Post-/Long-COVID Symptoms, Vaccination and Functional Status—Findings from a State-Wide Online Screening Study

by Sonia Lippke, Robin Rinn, Christina Derksen and Alina Dahmen

Vaccines 2023, 11(3), 691; https://doi.org/10.3390/vaccines11030691 - 17 Mar 2023

Cited by 2 | Viewed by 2243

Abstract

(1) Background: Better understanding of post-/long-COVID and limitations in daily life due to the symptoms as well as the preventive potential of vaccinations is required. It is unclear whether the number of doses and timepoint interrelate with the trajectory of post-/long-COVID. Accordingly, we examined how many patients positively screened with post-/long-COVID were vaccinated and whether the vaccination status and the timepoint of vaccination in relation to the acute infection were related to post-/long-COVID symptom severity and patients’ functional status (i.e., perceived symptom severity, social participation, workability, and life satisfaction) over time. (2) Methods: 235 patients suffering from post-/long-COVID were recruited into an online survey in Bavaria, Germany, and assessed at baseline (T1), after approximately three weeks (T2), and approximately four weeks (T3). (3) Results: 3.5% were not vaccinated, 2.3% were vaccinated once, 20% twice, and 53.3% three times. Overall, 20.9% did not indicate their vaccination status. The timepoint of vaccination was related to symptom severity at T1, and symptoms decreased significantly over time. Being vaccinated more often was associated with lower life satisfaction and workability at T2. (4) Conclusions: This study provides evidence to get vaccinated against SARS-CoV-2, as it has shown that symptom severity was lower in those patients who were vaccinated prior to the infection compared to those getting infected prior to or at the same time of the vaccination. However, the finding that being vaccinated against SARS-CoV-2 more often correlated with lower life satisfaction and workability requires more attention. There is still an urgent necessity for appropriate treatment for overcoming long-/post-COVID symptoms efficiently. Vaccination can be part of prevention measures, and there is still a need for a communication strategy providing objective information about the usefulness and risks of vaccinations. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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12 pages, 1451 KiB

Open AccessArticle

COVID-19 Vaccine Booster Shot Preserves T Cells Immune Response Based on Interferon-Gamma Release Assay in Inflammatory Bowel Disease (IBD) Patients on Anti-TNFα Treatment

by Grazia Pavia, Rocco Spagnuolo, Angela Quirino, Nadia Marascio, Aida Giancotti, Silvio Simeone, Cristina Cosco, Elena Tino, Federico Carrabetta, Gianfranco Di Gennaro, Carmelo Nobile, Aida Bianco, Giovanni Matera and Patrizia Doldo

Vaccines 2023, 11(3), 591; https://doi.org/10.3390/vaccines11030591 - 3 Mar 2023

Cited by 7 | Viewed by 2116

Abstract

Immune-modifying treatment in inflammatory bowel disease (IBD) impairs the humoral response. The role of T lymphocytes in this setting is still unclear. This study aims to assess if a booster shot (third dose) of BNT162b2 mRNA COVID-19 vaccine enhanced the humoral response and elicited cellular immunity in IBD patients on different immuno-therapy regimens compared to healthy controls (HCs). Five months after a booster dose, serological and T-cell responses were assessed. The measurements were described using geometric means with 95% confidence intervals. The differences between study groups were assessed by Mann–Whitney tests. Seventy-seven subjects (n = 53 IBD patients and n = 24 HCs), who were fully vaccinated and not previously SARS-CoV-2 infected, were recruited. Regarding the IBD patients, 19 were affected by Crohn’s disease and 34 by ulcerative colitis. During the vaccination cycle, half of the patients (53%) were on stable treatment with aminosalicylates, and 32% were on biological therapy. No differences in antibody concentrations between IBD patients and HCs, nor T-cell responses, were found. Stratifying IBD patients based on the type of treatment (anti-TNFα agents vs. other treatment regimens), a decrease only in antibody titer (p = 0.008), but not in cellular response, was observed. Even after the COVID-19 vaccine booster dose, the TNFα inhibitors selectively decreased the humoral immune response compared to patients on other treatment regimens. The T-cell response was preserved in all study groups. These findings highlight the importance of evaluating T-cell immune responses following COVID-19 vaccination in a routine diagnostic setting, particularly for immunocompromised cohorts. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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8 pages, 645 KiB

Open AccessCommunication

Transient Positive SARS-CoV-2 PCR without Induction of Systemic Immune Responses

by Barbara C. Gärtner, Verena Klemis, Tina Schmidt, Martina Sester and Tim Meyer

Vaccines 2023, 11(2), 482; https://doi.org/10.3390/vaccines11020482 - 19 Feb 2023

Viewed by 1992

Abstract

SARS-CoV-2 testing is dominated by PCR to guide treatment and individual as well as public health preventive measures. Among 1700 football (soccer) players and staff of the German Bundesliga and Bundesliga 2 who were regularly tested by PCR twice weekly, 98 individuals had a positive PCR (May 2020 to mid-January 2021). A subset of these were retested shortly after the initial positive result. Among those, 11 subjects were identified who only had a transient single positive PCR of low viral load. All individuals were asymptomatic and none developed long COVID. We tested SARS-CoV-2 IgG and IgA as well as SARS-CoV-2 specific CD4 und CD8 positive T cells, and showed that only one out of 11 individuals developed SARS-CoV-2 specific cellular and humoral immunity after the positive PCR, whereas a specific immunity was undetectable in all other individuals. Thus, a single positive PCR might indicate that transient colonization of the upper respiratory tract with SARS-CoV-2 may occur without systemic induction of specific adaptive immunity. Together with test artifacts as another potential reason for a transiently positive test, this finding may favor cautious interpretation of positive PCR results or retesting before initiating intervening treatment or infection control measures in some cases. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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11 pages, 3339 KiB

Open AccessCommunication

Differential Loss of OAS Genes Indicates Diversification of Antiviral Immunity in Mammals

by Leopold Eckhart and Wolfgang Sipos

Vaccines 2023, 11(2), 419; https://doi.org/10.3390/vaccines11020419 - 12 Feb 2023

Cited by 1 | Viewed by 2633

Abstract

One of the main mechanisms of inducing an antiviral response depends on 2′-5′-oligoadenylate synthetases (OAS), which sense double-stranded RNA in the cytoplasm and activate RNase L. Mutations leading to the loss of functional OAS1 and OAS2 genes have been identified as important modifiers of the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we performed comparative genomics to search for inactivating mutations of OAS genes in other species of mammals and to establish a model for the diversifying evolution of the OAS gene family. We found that a recombination of the OAS and OAS-like (OASL) loci has led to the loss of OAS2 in camelids, which also lack OAS3. Both paralogs of OASL and OAS3 are absent in Asian pangolins. An evolutionarily ancient OAS paralog, which we tentatively name OAS4, has been lost in pangolins, bats and humans. A previously unknown OAS gene, tentatively named OAS5, is present in Yangochiroptera, a suborder of bats. These differences in the OAS gene repertoire may affect innate immune responses to coronaviruses and other RNA viruses. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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Graphical abstract

30 pages, 2122 KiB

Open AccessArticle

Modelling of the Innate and Adaptive Immune Response to SARS Viral Infection, Cytokine Storm and Vaccination

by Cristina Leon, Alexey Tokarev, Anass Bouchnita and Vitaly Volpert

Vaccines 2023, 11(1), 127; https://doi.org/10.3390/vaccines11010127 - 4 Jan 2023

Cited by 13 | Viewed by 3461

Abstract

In this work, we develop mathematical models of the immune response to respiratory viral infection, taking into account some particular properties of the SARS-CoV infections, cytokine storm and vaccination. Each model consists of a system of ordinary differential equations that describe the interactions of the virus, epithelial cells, immune cells, cytokines, and antibodies. Conventional analysis of the existence and stability of stationary points is completed by numerical simulations in order to study the dynamics of solutions. The behavior of the solutions is characterized by large peaks of virus concentration specific to acute respiratory viral infections. At the first stage, we study the innate immune response based on the protective properties of interferon secreted by virus-infected cells. Viral infection down-regulates interferon production. This competition can lead to the bistability of the system with different regimes of infection progression with high or low intensity. After that, we introduce the adaptive immune response with antigen-specific T- and B-lymphocytes. The resulting model shows how the incubation period and the maximal viral load depend on the initial viral load and the parameters of the immune response. In particular, an increase in the initial viral load leads to a shorter incubation period and higher maximal viral load. The model shows that a deficient production of antibodies leads to an increase in the incubation period and even higher maximum viral loads. In order to study the emergence and dynamics of cytokine storm, we consider proinflammatory cytokines produced by cells of the innate immune response. Depending on the parameters of the model, the system can remain in the normal inflammatory state specific for viral infections or, due to positive feedback between inflammation and immune cells, pass to cytokine storm characterized by the excessive production of proinflammatory cytokines. Finally, we study the production of antibodies due to vaccination. We determine the dose–response dependence and the optimal interval of vaccine dose. Assumptions of the model and obtained results correspond to the experimental and clinical data. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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14 pages, 3679 KiB

Open AccessArticle

Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report

by Jason D. Goldman, Kai Wang, Katharina Röltgen, Sandra C. A. Nielsen, Jared C. Roach, Samia N. Naccache, Fan Yang, Oliver F. Wirz, Kathryn E. Yost, Ji-Yeun Lee, Kelly Chun, Terri Wrin, Christos J. Petropoulos, Inyoul Lee, Shannon Fallen, Paula M. Manner, Julie A. Wallick, Heather A. Algren, Kim M. Murray, Jennifer Hadlock, Daniel Chen, Chengzhen L. Dai, Dan Yuan, Yapeng Su, Joshua Jeharajah, William R. Berrington, George P. Pappas, Sonam T. Nyatsatsang, Alexander L. Greninger, Ansuman T. Satpathy, John S. Pauk, Scott D. Boyd and James R. Heath Show full author list Hide full author list

Vaccines 2023, 11(1), 5; https://doi.org/10.3390/vaccines11010005 - 20 Dec 2022

Cited by 42 | Viewed by 2925

Abstract

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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Graphical abstract

9 pages, 1615 KiB

Open AccessArticle

Quantitative Analysis of Anti-N and Anti-S Antibody Titers of SARS-CoV-2 Infection after the Third Dose of COVID-19 Vaccination

by Nuri Lee, Seri Jeong, Su Kyung Lee, Eun-Jung Cho, Jungwon Hyun, Min-Jeong Park, Wonkeun Song and Hyun Soo Kim

Vaccines 2022, 10(7), 1143; https://doi.org/10.3390/vaccines10071143 - 18 Jul 2022

Cited by 25 | Viewed by 2517

Abstract

We quantitatively analyzed SARS-CoV-2 antibody levels in patients after two doses of the ChAdOx1 nCoV-19 vaccine and the third BNT162b2 booster. We obtained 255 serum samples from 149 healthcare workers 1 and 4 months after the third dose. Of the 149 participants, 58 (38.9%) experienced COVID-19 infection during the 4-month study period, with infection occurring 7–62 days before the second blood draw. Total antibody titers against the anti-spike (anti-S) and anti-nucleocapsid (anti-N) proteins of SARS-CoV-2 were measured using Elecsys Anti-SARS-CoV-2 S and Elecsys Anti-SARS-CoV-2 assays (Roche), respectively. The median anti-S antibody titer in the non-infected groups at 4 months after the third dose was significantly decreased compared to that at 1 month after the third dose (from 17,777 to 3673 U/mL, p < 0.001). The infected group showed higher median anti-S antibody titers at 4 months (19,539 U/mL) than the non-infected group (3673 U/mL). The median anti-N antibody titer in the infected group at 4 months after the third dose was a 5.07 cut-off index (79.3% positivity). Anti-N antibody titers in the infected group were correlated with the number of days after SARS-CoV-2 infection. These data provide useful information for determining quarantine strategies and fourth vaccination requirements. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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16 pages, 1361 KiB

Open AccessArticle

The T Cell Epitope Landscape of SARS-CoV-2 Variants of Concern

by Simen Tennøe, Marius Gheorghe, Richard Stratford and Trevor Clancy

Vaccines 2022, 10(7), 1123; https://doi.org/10.3390/vaccines10071123 - 14 Jul 2022

Cited by 5 | Viewed by 2189

Abstract

During the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOC) emerged, bringing with them varying degrees of health and socioeconomic burdens. In particular, the Omicron VOC displayed distinct features of increased transmissibility accompanied by antigenic drift in the spike protein that partially circumvented the ability of pre-existing antibody responses in the global population to neutralize the virus. However, T cell immunity has remained robust throughout all the different VOC transmission waves and has emerged as a critically important correlate of protection against SARS-CoV-2 and its VOCs, in both vaccinated and infected individuals. Therefore, as SARS-CoV-2 VOCs continue to evolve, it is crucial that we characterize the correlates of protection and the potential for immune escape for both B cell and T cell human immunity in the population. Generating the insights necessary to understand T cell immunity, experimentally, for the global human population is at present a critical but a time consuming, expensive, and laborious process. Further, it is not feasible to generate global or universal insights into T cell immunity in an actionable time frame for potential future emerging VOCs. However, using computational means we can expedite and provide early insights into the correlates of T cell protection. In this study, we generated and revealed insights on the T cell epitope landscape for the five main SARS-CoV-2 VOCs observed to date. We demonstrated using a unique AI prediction platform, a significant conservation of presentable T cell epitopes across all mutated peptides for each VOC. This was modeled using the most frequent HLA alleles in the human population and covers the most common HLA haplotypes in the human population. The AI resource generated through this computational study and associated insights may guide the development of T cell vaccines and diagnostics that are even more robust against current and future VOCs, and their emerging subvariants. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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Review

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20 pages, 1362 KiB

Open AccessReview

Insights into the Scenario of SARS-CoV-2 Infection in Male Reproductive Toxicity

by Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan, Sandra Kannampuzha, Reshma Murali, Arunraj Namachivayam, Raja Ganesan, Kaviyarasi Renu, Abhijit Dey, Balachandar Vellingiri and D. S. Prabakaran

Vaccines 2023, 11(3), 510; https://doi.org/10.3390/vaccines11030510 - 22 Feb 2023

Cited by 7 | Viewed by 3023 | Correction

Abstract

COVID-19 has become a significant public health concern that has catastrophic consequences for society. Some preliminary evidence suggests that the male reproductive system may be an infection target for SARS-CoV-2. SARS-CoV-2 may be transmitted sexually, according to preliminary research. Testicular cells exhibit a high level of the angiotensin-converting enzyme 2 (ACE2) receptor, which enhances the entry of the SARS-CoV-2 into host cells. Some instances of COVID-19 have been documented to exhibit hypogonadism during the acute stage. Furthermore, systemic inflammatory reactions triggered by SARS-CoV-2 infection may cause oxidative stress (OS), which has been shown to have profoundly deleterious consequences on testicular functioning. This work gives a clear picture of how COVID-19 may affect male reproductive systems and calls attention to the many unanswered questions about the mechanisms by which this virus can be linked to men’s health and fertility. Full article

(This article belongs to the Special Issue Immune Response of SARS-CoV-2 Infection)

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