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Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: closed (3 March 2023) | Viewed by 60719

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Dr. Hatem A. Elshabrawy

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Department of Molecular and Cellular Biology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA
Interests: development of antiviral small molecules and antibodies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Coronaviruses (CoVs) are RNA viruses that have been a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. Currently, the world is concerned about SARS-CoV-2, the causative agent of COVID-19, which was initially identified in the city of Wuhan, China, in December 2019. Tens of thousands of cases and several thousand deaths have been reported in many countries. SARS-CoV-2 is highly contagious based on the number of infected cases to date. There is a need for development of vaccines and effective therapeutics that can control the current outbreak.

We are interested in manuscripts that focus on the replication, viral life cycle, and pathogenesis of SARS-CoV-2. We are also interested in areas of identification of novel drug targets and the development of vaccines and therapeutics for COVID-19. We aim to publish a variety of manuscripts that represent different research studies that investigate unique aspects of viral pathogenesis and life cycle and identify/test different vaccines and antivirals for efficacy against SARS-CoV-2.

Dr. Hatem A. Elshabrawy
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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Vaccine
SARS-CoV-2
COVID-19
Antibodies
Antivirals

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Published Papers (10 papers)

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10 pages, 1077 KiB

Open AccessCommunication

Determining the SARS-CoV-2 Anti-Spike Cutoff Level Denoting Neutralizing Activity Using Two Commercial Kits

by Engy Mohamed El-Ghitany, Mona H. Hashish, Azza Galal Farghaly and Eman A. Omran

Vaccines 2022, 10(11), 1952; https://doi.org/10.3390/vaccines10111952 - 18 Nov 2022

Cited by 3 | Viewed by 1781

Abstract

Background: The viral neutralization assay is the gold standard to estimate the level of immunity against SARS-CoV-2. This study analyzes the correlation between the quantitative Anti-SARS-CoV-2 QuantiVac ELISA (IgG) and the NeutraLISA neutralization assay. Methods: 650 serum samples were tested for both SARS-CoV-2 anti-spike (anti-S) immunoglobulin G (IgG) and neutralizing antibodies (nAbs) using kits by EUROIMMUN, Germany. Results: There was a significant correlation between levels of anti-S and nAbs (Spearman’s rho = 0.913). Among the positive samples for anti-S, 77.0% (n = 345) were positive for nAbs. There was a substantial agreement between anti-S and nAbs (Cohen’s kappa coefficient = 0.658; agreement of 83.38%). Considering NeutraLISA as a gold standard, anti-S had a sensitivity of 98.57%, specificity of 65.66%, NPV of 97.5%, and PPV of 77.0%. When the anti-S titer was greater than 18.1 RU/mL (57.9 BAU/mL), nAbs were positive, with a sensitivity of 90.0% and specificity of 91%. Conclusions: A titer of SARS-CoV-2 anti-S IgG can be correlated with levels of nAbs. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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21 pages, 5225 KiB

Open AccessArticle

Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations

by Daisuke Hisamatsu, Akari Ikeda, Lisa Ito, Yasushi Matsushita, Makoto Hiki, Hirotake Mori, Yoko Tabe, Toshio Naito and Chihiro Akazawa

Vaccines 2022, 10(11), 1815; https://doi.org/10.3390/vaccines10111815 - 28 Oct 2022

Viewed by 2242

Abstract

To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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16 pages, 3609 KiB

Open AccessArticle

A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titers

by Patrick McCarthy, Joseph A. Pathakamuri, Daniel Kuebler, Jocelyn Neves, Madison Krohn, Michael Rohall, Isaac Archibeque, Heidi Giese, Martina Werner, Eugenio Daviso and Ulrich Thomann

Vaccines 2022, 10(10), 1760; https://doi.org/10.3390/vaccines10101760 - 20 Oct 2022

Cited by 3 | Viewed by 2552

Abstract

The COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyze patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not trivial; this process requires a visit to the doctor’s office, a professionally trained phlebotomist to draw several milliliters of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. A novel whole blood collection kit (truCOLLECT) allows for a lancet-based, decentralized capillary blood collection of metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS-CoV-2 spike (total and neutralizing) and nucleocapsid protein antibody titers in plasma samples obtained via venipuncture were compared to antibodies extracted from desiccated whole blood using Adaptive Focused Acoustics (AFA). Paired plasma versus desiccated blood extracts yields Pearson correlation coefficients of 0.98; 95% CI [0.96, 0.99] for anti-SARS-CoV-2 spike protein antibodies, 0.97; 95% CI [0.95, 0.99] for neutralizing antibodies, and 0.97; 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies. These data suggest that serology testing using desiccated and stabilized whole blood samples can be a convenient and cost-effective alternative to phlebotomy. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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17 pages, 2369 KiB

Open AccessArticle

Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2

by Zsofia Hevesi, Daniela Anna Gerges, Sebastian Kapps, Raimundo Freire, Sophie Schmidt, Daniela D. Pollak, Klaus Schmetterer, Tobias Frey, Rita Lang, Wolfgang Winnicki, Alice Schmidt, Tibor Harkany and Ludwig Wagner

Vaccines 2022, 10(4), 516; https://doi.org/10.3390/vaccines10040516 - 26 Mar 2022

Cited by 3 | Viewed by 2965

Abstract

First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either E. coli or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10⁻⁴–10⁻⁵) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4⁺ and CD8⁺ T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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19 pages, 1022 KiB

Open AccessArticle

Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines

by Xuhua Xia

Vaccines 2021, 9(7), 734; https://doi.org/10.3390/vaccines9070734 - 3 Jul 2021

Cited by 98 | Viewed by 29211

Abstract

The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5′-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5′-UTR and the downstream 3′-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine (

Ψ

) complicates some of these optimization processes because

Ψ

is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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Review

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14 pages, 446 KiB

Open AccessFeature PaperReview

The Effects of Heterologous Immunization with Prime-Boost COVID-19 Vaccination against SARS-CoV-2

by Tzu-Chuan Ho, Yi-Ming Arthur Chen, Hung-Pin Chan, Chin-Chuan Chang, Kuo-Pin Chuang, Che-Hsin Lee, Cheng-Hui Yuan, Yu-Chang Tyan and Ming-Hui Yang

Vaccines 2021, 9(10), 1163; https://doi.org/10.3390/vaccines9101163 - 11 Oct 2021

Cited by 29 | Viewed by 5622

Abstract

Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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8 pages, 832 KiB

Open AccessCase Report

Resistance towards ChadOx1 nCoV-19 in an 83 Years Old Woman Experiencing Vaccine Induced Thrombosis with Thrombocytopenia Syndrome

by Constant Gillot, Julien Favresse, Vincent Maloteau, Valérie Mathieux, Jean-Michel Dogné, François Mullier and Jonathan Douxfils

Vaccines 2022, 10(12), 2056; https://doi.org/10.3390/vaccines10122056 - 30 Nov 2022

Viewed by 1938

Abstract

Background: in this report, we describe the case of an 83-year-old woman vaccinated with ChadOx1 nCoV-19 who developed a so-called vaccine-induced thrombosis with thrombocytopenia syndrome and who did not develop any antibodies against the spike protein of SARS-CoV-2 at 30 days following the administration of her first dose of ChadOx1 nCoV-19. Experimental section: two serum samples from the patient and 5 serum samples from 5 control individuals having received the two-dose regimen vaccination with ChadOx1 nCoV-19 were evaluated. In order to investigate the lack of response to the vaccination, a cell model was developed. This model permits to evaluate the interaction between responsive cells (A549) possessing the Coxsackievirus and Adenovirus Receptor (CAR), a defined concentration of ChadOx1 nCoV-19 and serial dilution of the patient or the control serum. The aim was to assess the impact of these sera on the production of the spike (S) protein induced by the transfection of the genetic material of ChadOx1 nCoV-19 into the A549 cells. The S protein is measured in the supernatant using an ELISA technique. Results: interestingly, the serum from the patient who developed the vaccine-induced thrombosis with thrombocytopenia syndrome impaired the production of S protein by the A549 cells transfected with ChadOx1 nCoV-19. This was not observed with the controls who did not interfere with the transfection of ChadOx1 nCoV-19 into A549 cells since the S protein is retrieved in the supernatant fraction. Conclusion: based on the data coming from the clinical and the cell model information, we found a possible explanation on the absence of antibody response in our patient. She has, or has developed, characteristics that prevent the production of the S protein in contrast to control subjects. We were not able to investigate the entire mechanism behind this resistance which deserve further investigations. A link between this resistance and the development of the thrombosis with thrombocytopenia syndrome following vaccination with ChadOx1 nCoV-19 cannot be excluded. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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7 pages, 1001 KiB

Open AccessBrief Report

SARS-CoV-2 Neutralizing Antibodies in Chile after a Vaccination Campaign with Five Different Schemes

by Ximena Aguilera, Juan Hormazábal, Cecilia Vial, Lina Jimena Cortes, Claudia González, Paola Rubilar, Mauricio Apablaza, Muriel Ramírez-Santana, Gloria Icaza, Loreto Nuñez-Franz, Carla Castillo-Laborde, Carolina Ramírez-Riffo, Claudia Pérez, Rubén Quezada-Gate, Macarena Said and Pablo Vial

Vaccines 2022, 10(7), 1051; https://doi.org/10.3390/vaccines10071051 - 30 Jun 2022

Cited by 5 | Viewed by 1957

Abstract

Using levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines different vaccine technologies and heterologous boosters. From a population-based study performed in November 2021, we randomly selected 120 seropositive individuals, organized into six groups of positive samples (20 subjects each) according to natural infection history and the five most frequent vaccination schemes. We conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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22 pages, 958 KiB

Open AccessCase Report

Acquired Thrombotic Thrombocytopenic Purpura Following Inactivated COVID-19 Vaccines: Two Case Reports and a Short Literature Review

by Imen Ben Saida, Iyed Maatouk, Radhouane Toumi, Emna Bouslama, Hajer Ben Ismail, Chaker Ben Salem and Mohamed Boussarsar

Vaccines 2022, 10(7), 1012; https://doi.org/10.3390/vaccines10071012 - 24 Jun 2022

Cited by 11 | Viewed by 2756

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in December 2019, causing millions of deaths all over the world, and the lack of specific treatment for severe forms of coronavirus disease 2019 (COVID-19) have led to the development of vaccines in record time, increasing the risk of vaccine safety issues. Recently, several cases of thrombotic thrombocytopenic purpura (TTP) have been reported following COVID-19 vaccination. TTP is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and ischemic end-organ lesions. It can be either congenital or acquired. Various events such as viral infections, medication, pregnancy, malignancies, and vaccinations may cause TTP. Here, we report two cases of acquired TTP following Sinopharm COVID-19 vaccine (BBIBP-CorV) and Sinovac COVID-19 vaccine (CoronaVac). Diagnosis was based on clinical presentation and confirmed with a severe reduction in the activity of von Willebrand factor-cleaving protease ADAMTS-13 and the presence of inhibitory autoantibodies. The two patients were successfully treated with corticosteroids, plasma exchange therapy and rituximab in the acute phase. In the literature, the reported cases of TTP induced by COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based COVID-19 vaccines. To the best of our knowledge, this is the first report of acquired TTP after inactivated virus COVID-19 vaccination. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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5 pages, 18067 KiB

Open AccessCase Report

Development of Flat Warts on the Cheeks after BioNTech-Pfizer BNT162b2 Vaccine: Is There a Correlation?

by Gerardo Cazzato, Paolo Romita, Caterina Foti, Debora Lobreglio, Irma Trilli, Anna Colagrande, Giuseppe Ingravallo and Leonardo Resta

Vaccines 2022, 10(4), 532; https://doi.org/10.3390/vaccines10040532 - 29 Mar 2022

Cited by 4 | Viewed by 8119

Abstract

The SARS-CoV-2 pandemic has affected health systems across the globe, making the use of vaccines more urgent and topical than ever. Since the first months after the introduction of vaccinations, several reactions, both local and systemic, have been reported although they were mostly very mild and only rarely harbingers of more serious complications. We present a case of multiple flat warts onset over the cheeks in a patient after the second dose of mRNA BioNTech-Pfizer BNT162b2 vaccine, and we discuss the possible temporal association between the two events, also considering the patient’s antibody status. Full article

(This article belongs to the Special Issue Unraveling SARS-CoV-2 Pathogenesis: Development of Vaccines and Therapeutics for COVID-19: Version II)

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