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15 pages, 24222 KiB

Open AccessArticle

Design and Assessment of a Novel In Silico Approach for Developing a Next-Generation Multi-Epitope Universal Vaccine Targeting Coronaviruses

by Muhammad Asif Rasheed, Sohail Raza, Wadi B. Alonazi, Muhammad Adnan Ashraf, Muhammad Tariq Navid, Irfana Aslam, Muhammad Nasir Iqbal, Sarfraz Ur Rahman and Muhammad Ilyas Riaz

Microorganisms 2023, 11(9), 2282; https://doi.org/10.3390/microorganisms11092282 - 11 Sep 2023

Viewed by 1768

Abstract

In the past two decades, there have been three coronavirus outbreaks that have caused significant economic and health crises. Biologists predict that more coronaviruses may emerge in the near future. Therefore, it is crucial to develop preventive vaccines that can effectively combat multiple [...] Read more.

In the past two decades, there have been three coronavirus outbreaks that have caused significant economic and health crises. Biologists predict that more coronaviruses may emerge in the near future. Therefore, it is crucial to develop preventive vaccines that can effectively combat multiple coronaviruses. In this study, we employed computational approaches to analyze genetically related coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, focusing on the spike glycoprotein as a potential vaccine candidate. By predicting common epitopes, we identified the top epitopes and combined them to create a multi-epitope candidate vaccine. The overall quality of the candidate vaccine was validated through in silico analyses, confirming its antigenicity, immunogenicity, and stability. In silico docking and simulation studies suggested a stable interaction between the multi-epitope candidate vaccine and human toll-like receptor 2 (TLR2). In silico codon optimization and cloning were used to further explore the successful expression of the designed candidate vaccine in a prokaryotic expression system. Based on computational analysis, the designed candidate vaccine was found to be stable and non-allergenic in the human body. The efficiency of the multi-epitope vaccine in triggering effective cellular and humoral immune responses was assessed through immune stimulation, demonstrating that the designed candidate vaccine can elicit specific immune responses against multiple coronaviruses. Therefore, it holds promise as a potential candidate vaccine against existing and future coronaviruses. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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18 pages, 2879 KiB

Open AccessArticle

A Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Immunoglobulin G Assay: A Robust Method for Evaluation of Vaccine Immunogenicity Using an Established Correlate of Protection

by Mingzhu Zhu, Shane Cloney-Clark, Sheau-line Feng, Anand Parekh, Drew Gorinson, David Silva, Paul Skonieczny, Adjele Wilson, Raj Kalkeri, Wayne Woo, Miranda R. Cai, Louis Fries, Greg Glenn and Joyce S. Plested

Microorganisms 2023, 11(7), 1789; https://doi.org/10.3390/microorganisms11071789 - 11 Jul 2023

Cited by 6 | Viewed by 1667

Abstract

As the COVID-19 pandemic continues, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge. Immunogenicity evaluation of vaccines and identification of correlates of protection for vaccine effectiveness is critical to aid the development of vaccines against emerging variants. Anti-recombinant spike [...] Read more.

As the COVID-19 pandemic continues, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge. Immunogenicity evaluation of vaccines and identification of correlates of protection for vaccine effectiveness is critical to aid the development of vaccines against emerging variants. Anti-recombinant spike (rS) protein immunoglobulin G (IgG) quantitation in the systemic circulation (serum/plasma) is shown to correlate with vaccine efficacy. Thus, an enzyme-linked immunosorbent assay (ELISA)-based binding assay to detect SARS-CoV-2 (ancestral and variant strains) anti-rS IgG in human serum samples was developed and validated. This assay successfully met acceptance criteria for inter/intra-assay precision, specificity, selectivity, linearity, lower/upper limits of quantitation, matrix effects, and assay robustness. The analyte in serum was stable for up to 8 freeze/thaw cycles and 2 years in −80 °C storage. Similar results were observed for the Beta, Delta, and Omicron BA.1/BA.5/XBB.1.5 variant-adapted assays. Anti-rS IgG assay results correlated significantly with neutralization and receptor binding inhibition assays. In addition, usage of international reference standards allows data extrapolation to WHO international units (BAU/mL), facilitating comparison of results with other IgG assays. This anti-rS IgG assay is a robust, high-throughput method to evaluate binding IgG responses to S protein in serum, enabling rapid development of effective vaccines against emerging COVID-19 variants. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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20 pages, 3568 KiB

Open AccessArticle

Identification of Z-Tyr-Ala-CHN₂, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2

by Jordi Doijen, Koen Temmerman, Christel Van den Eynde, Annick Diels, Nick Van den Broeck, Michiel Van Gool, Inha Heo, Steffen Jaensch, Marleen Zwaagstra, Mayra Diosa Toro, Winston Chiu, Steven De Jonghe, Pieter Leyssen, Denisa Bojkova, Sandra Ciesek, Jindrich Cinatl, Lore Verschueren, Christophe Buyck, Frank Van Kuppeveld, Johan Neyts, Marnix Van Loock and Ellen Van Damme Show full author list Hide full author list

Microorganisms 2023, 11(3), 717; https://doi.org/10.3390/microorganisms11030717 - 10 Mar 2023

Cited by 2 | Viewed by 3062

Abstract

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a [...] Read more.

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN₂, which was identified in a cell-based antiviral screen. The molecule exerts sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. Time-of-addition studies reveal that Z-Tyr-Ala-CHN₂ acts at the early phase of the infection cycle, which is in line with the observation that the molecule inhibits cathepsin L. This results in antiviral activity against SARS-CoV-2 in VeroE6, A549-hACE2, and HeLa-hACE2 cells, but not in Caco-2 cells or primary human nasal epithelial cells since the latter two cell types also permit entry via transmembrane protease serine subtype 2 (TMPRSS2). Given their cell-specific activity, cathepsin L inhibitors still need to prove their value in the clinic; nevertheless, the activity profile of Z-Tyr-Ala-CHN₂ makes it an interesting tool compound for studying the biology of coronavirus entry and replication. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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10 pages, 1100 KiB

Open AccessArticle

Cross-Reactivity of Antibodies in Intravenous Immunoglobulin Preparation for Protection against SARS-CoV-2

by Toshifumi Osaka, Yoko Yamamoto, Takehisa Soma, Naoko Yanagisawa and Satoru Nagata

Microorganisms 2023, 11(2), 471; https://doi.org/10.3390/microorganisms11020471 - 13 Feb 2023

Cited by 1 | Viewed by 2646

Abstract

Severe cases of COVID-19 continue to put pressure on medical operations by prolonging hospitalization, occupying intensive care beds, and forcing medical personnel to undergo harsh labor. The eradication of SARS-CoV-2 through vaccine development has yet to be achieved, mainly due to the appearance [...] Read more.

Severe cases of COVID-19 continue to put pressure on medical operations by prolonging hospitalization, occupying intensive care beds, and forcing medical personnel to undergo harsh labor. The eradication of SARS-CoV-2 through vaccine development has yet to be achieved, mainly due to the appearance of multiple mutant-incorporating strains. The present study explored the utility of human intravenous immunoglobulin (IVIG) preparations in suppressing the aggravation of any COVID-19 infection using a SARS-CoV-2 pseudovirus assay. Our study revealed the existence of IgG antibodies in human IVIG preparations, which recognized the spike protein of SARS-CoV-2. Remarkably, the pretreatment of ACE2/TMPRSS2-expressing host cells (HEK293T cells) with IVIG preparations (10 mg/mL) inhibited approximately 40% entry of SARS-CoV-2 pseudovirus even at extremely low concentrations of IgG (0.16–1.25 mg/mL). In contrast, the antibody-dependent enhancement of viral entry was confirmed when SARS-CoV-2 pseudovirus was treated with some products at an IgG concentration of 10 mg/mL. Our data suggest that IVIG may contribute to therapy for COVID-19, including for cases caused by SARS-CoV-2 variants, since IVIG binds not only to the spike proteins of the virus, but also to human ACE2/TMPRSS2. An even better preventive effect can be expected with blood collected after the start of the COVID-19 pandemic. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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14 pages, 1580 KiB

Open AccessArticle

Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation

by Joyce S. Plested, Mingzhu Zhu, Shane Cloney-Clark, Edmond Massuda, Urvashi Patel, Andrew Klindworth, Michael J. Massare, Rongman Cai, Louis Fries, Greg Glenn and Raj Kalkeri

Microorganisms 2023, 11(2), 368; https://doi.org/10.3390/microorganisms11020368 - 1 Feb 2023

Cited by 4 | Viewed by 1894

Abstract

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to [...] Read more.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials. Inter- and intra-assay precision, specificity, linearity, lower limit of quantitation, and assay robustness parameters successfully met the acceptance criteria. Heme and lipid matrix effects showed minimal interference on the assay. Samples were stable for testing in the assay even with 8 freeze/thaws and up to 24 months in −80 °C storage. The assay was also adapted for variants (Delta and Omicron BA.1/BA.5), with similar validation results. The hACE2 assay showed significant correlation with anti-recombinant S immunoglobulin G levels and neutralizing antibody titers. This assay provides a rapid, high-throughput option to evaluate vaccine immunogenicity. Along with other clinical biomarkers, it can provide valuable insights into immune evasion and correlates of protection and enable vaccine development against emerging COVID-19 variants. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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15 pages, 1210 KiB

Open AccessArticle

Remdesivir Influence on SARS-CoV-2 RNA Viral Load Kinetics in Nasopharyngeal Swab Specimens of COVID-19 Hospitalized Patients: A Real-Life Experience

by Laura Campogiani, Marco Iannetta, Andrea Di Lorenzo, Marta Zordan, Pier Giorgio Pace, Luigi Coppola, Mirko Compagno, Vincenzo Malagnino, Elisabetta Teti, Massimo Andreoni and Loredana Sarmati

Microorganisms 2023, 11(2), 312; https://doi.org/10.3390/microorganisms11020312 - 25 Jan 2023

Cited by 2 | Viewed by 1935

Abstract

There are still conflicting data on the virological effects of the SARS-CoV-2 direct antivirals used in clinical practice, in spite of the documented clinical efficacy. The aim of this monocentric retrospective study was to compare virologic and laboratory data of patients admitted due [...] Read more.

There are still conflicting data on the virological effects of the SARS-CoV-2 direct antivirals used in clinical practice, in spite of the documented clinical efficacy. The aim of this monocentric retrospective study was to compare virologic and laboratory data of patients admitted due to SARS-CoV-2 infection from March to December 2020 treated with either remdesivir (R), a protease inhibitor (lopinavir or darunavir/ritonavir (PI)) or no direct antiviral drugs (NT). Viral load variation was indirectly assessed through PCR cycle threshold (Ct) values on the nasopharyngeal swab, analyzing the results from swabs obtained at ward admission and 7 (±2) days later. Overall, 253 patients were included: patients in the R group were significantly older, more frequently males with a significantly higher percentage of severe COVID-19, requiring more often intensive care admission, compared to the other groups. Ct variation over time did not differ amongst the three treatment groups and did not seem to be influenced by corticosteroid use, even after normalization of the treatment groups for disease severity. Non-survivors had lower Ct on admission and showed a significantly slower viral clearance compared to survivors. CD4 T-lymphocytes absolute count assessed at ward admission correlated with a reduced Ct variation over time. In conclusion, viral clearance appears to be slower in COVID-19 non-survivors, while it seems not to be influenced by the antiviral treatment received. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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13 pages, 286 KiB

Open AccessArticle

Evaluation of Drug-Induced Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection

by Nicoleta Mihai, Catalin Tiliscan, Constanta Angelica Visan, Laurentiu Stratan, Oana Ganea, Stefan Sorin Arama, Mihai Lazar and Victoria Arama

Microorganisms 2022, 10(10), 2045; https://doi.org/10.3390/microorganisms10102045 - 17 Oct 2022

Cited by 6 | Viewed by 1633

Abstract

Elevated liver enzymes are frequently reported in SARS-CoV-2-infected patients. Several mechanisms of liver injury have been proposed, but no clear conclusions were drawn. We aimed to evaluate hepatocellular and cholestatic injury in relation to the administration of potentially hepatotoxic drugs included in the [...] Read more.

Elevated liver enzymes are frequently reported in SARS-CoV-2-infected patients. Several mechanisms of liver injury have been proposed, but no clear conclusions were drawn. We aimed to evaluate hepatocellular and cholestatic injury in relation to the administration of potentially hepatotoxic drugs included in the current COVID-19 therapeutic guidelines in a retrospective cohort of 396 hospitalized COVID-19 patients. The main findings of our study are: (1) Significant increase in aminotransferases level was observed during hospitalization, suggesting drug-related hepatotoxicity. (2) Tocilizumab was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal. (3) Anakinra was correlated with ALT values greater than three times the upper limit of normal. (4) Younger patients receiving tocilizumab or anakinra had a higher risk of hepatocellular injury. (5) The combination of favipiravir with tocilizumab was associated with AST values greater than three times the upper limit of normal and with an increase in direct bilirubin. (6) The administration of at least three potentially hepatotoxic drugs was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal, and with the increase in indirect bilirubin. (7) Remdesivir and favipiravir by themselves did not correlate with hepatocellular or cholestatic injury in our study cohort. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

27 pages, 1440 KiB

Open AccessArticle

Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19

by Frauke Assmus, Jean-Sélim Driouich, Rana Abdelnabi, Laura Vangeel, Franck Touret, Ayorinde Adehin, Palang Chotsiri, Maxime Cochin, Caroline S. Foo, Dirk Jochmans, Seungtaek Kim, Léa Luciani, Grégory Moureau, Soonju Park, Paul-Rémi Pétit, David Shum, Thanaporn Wattanakul, Birgit Weynand, Laurent Fraisse, Jean-Robert Ioset, Charles E. Mowbray, Andrew Owen, Richard M. Hoglund, Joel Tarning, Xavier de Lamballerie, Antoine Nougairède, Johan Neyts, Peter Sjö, Fanny Escudié, Ivan Scandale and Eric Chatelain Show full author list Hide full author list

Microorganisms 2022, 10(8), 1639; https://doi.org/10.3390/microorganisms10081639 - 12 Aug 2022

Cited by 4 | Viewed by 4863

Abstract

In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, [...] Read more.

In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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13 pages, 1130 KiB

Open AccessArticle

A Calculator for COVID-19 Severity Prediction Based on Patient Risk Factors and Number of Vaccines Received

by Ariel Israel, Alejandro A. Schäffer, Eugene Merzon, Ilan Green, Eli Magen, Avivit Golan-Cohen, Shlomo Vinker and Eytan Ruppin

Microorganisms 2022, 10(6), 1238; https://doi.org/10.3390/microorganisms10061238 - 16 Jun 2022

Cited by 3 | Viewed by 2831

Abstract

Vaccines have allowed for a significant decrease in COVID-19 risk, and new antiviral medications can prevent disease progression if given early in the course of the disease. The rapid and accurate estimation of the risk of severe disease in new patients is needed [...] Read more.

Vaccines have allowed for a significant decrease in COVID-19 risk, and new antiviral medications can prevent disease progression if given early in the course of the disease. The rapid and accurate estimation of the risk of severe disease in new patients is needed to prioritize the treatment of high-risk patients and maximize lives saved. We used electronic health records from 101,039 individuals infected with SARS-CoV-2, since the beginning of the pandemic and until 30 November 2021, in a national healthcare organization in Israel to build logistic models estimating the probability of subsequent hospitalization and death of newly infected patients based on a few major risk factors (age, sex, body mass index, hemoglobin A1C, kidney function, and the presence of hypertension, pulmonary disease, and malignancy) and the number of BNT162b2 mRNA vaccine doses received. The model’s performance was assessed by 10-fold cross-validation: the area under the curve was 0.889 for predicting hospitalization and 0.967 for predicting mortality. A total of 50%, 80%, and 90% of death events could be predicted with respective specificities of 98.6%, 95.2%, and 91.2%. These models enable the rapid identification of individuals at high risk for hospitalization and death when infected, and they can be used to prioritize patients to receive scarce medications or booster vaccination. The calculator is available online. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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7 pages, 1890 KiB

Open AccessCommunication

Ivermectin Does Not Protect against SARS-CoV-2 Infection in the Syrian Hamster Model

by Caroline S. Foo, Rana Abdelnabi, Laura Vangeel, Steven De Jonghe, Dirk Jochmans, Birgit Weynand and Johan Neyts

Microorganisms 2022, 10(3), 633; https://doi.org/10.3390/microorganisms10030633 - 16 Mar 2022

Cited by 5 | Viewed by 4825

Abstract

Ivermectin, an FDA-approved antiparasitic drug, has been reported to have in vitro activity against SARS-CoV-2. Increased off-label use of ivermectin for COVID-19 has been reported. We here assessed the effect of ivermectin in Syrian hamsters infected with the SARS-CoV-2 Beta (B.1.351) variant. Infected [...] Read more.

Ivermectin, an FDA-approved antiparasitic drug, has been reported to have in vitro activity against SARS-CoV-2. Increased off-label use of ivermectin for COVID-19 has been reported. We here assessed the effect of ivermectin in Syrian hamsters infected with the SARS-CoV-2 Beta (B.1.351) variant. Infected animals received a clinically relevant dose of ivermectin (0.4 mg/kg subcutaneously dosed) once daily for four consecutive days after which the effect was quantified. Ivermectin monotherapy did not reduce lung viral load and even significantly worsened SARS-CoV-2-induced lung pathology. Additionally, it did not potentiate the activity of molnupiravir (Lagevrio^TM) when combined with this drug. This study contributes to the growing body of evidence that ivermectin does not result in a beneficial effect in the treatment of COVID-19. These findings are important given the increasing, dangerous off-label use of ivermectin for the treatment of COVID-19. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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Review

Jump to: Research

17 pages, 1399 KiB

Open AccessReview

Protection against Severe Illness versus Immunity—Redefining Vaccine Effectiveness in the Aftermath of COVID-19

by Renuka Roche, Nouha H. Odeh, Abhay U. Andar, Mohan E. Tulapurkar and Joseph A. Roche

Microorganisms 2023, 11(8), 1963; https://doi.org/10.3390/microorganisms11081963 - 31 Jul 2023

Cited by 3 | Viewed by 2256

Abstract

Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get [...] Read more.

Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection. The answer to this question is consequential, not only to the understanding of how anti-SARS-CoV-2 vaccines work, but also to public health efforts against existing and novel pathogens. In this review, we argue that immune system sensitization-desensitization rather than sterilizing immunity may explain vaccine-mediated protection against severe COVID-19 illness even when the SARS-CoV-2 viral load is high. Through the lessons learned from COVID-19, we make the case that in the disease’s aftermath, public health agencies must revisit healthcare policies, including redefining the term “vaccine effectiveness.” Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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15 pages, 665 KiB

Open AccessReview

Challenges and Recent Advancements in COVID-19 Vaccines

by Shao-Cheng Wang, Chung-I Rai and Yuan-Chuan Chen

Microorganisms 2023, 11(3), 787; https://doi.org/10.3390/microorganisms11030787 - 18 Mar 2023

Cited by 5 | Viewed by 3940

Abstract

Vaccination is the most effective method for the prevention of COVID-19 caused by SARS-CoV-2, which is still a global epidemic. However, the evolution of SARS-CoV-2 is so rapid that various variants, including the Alpha, Beta, Gamma, Delta, and Omicron variants, have emerged, lowering [...] Read more.

Vaccination is the most effective method for the prevention of COVID-19 caused by SARS-CoV-2, which is still a global epidemic. However, the evolution of SARS-CoV-2 is so rapid that various variants, including the Alpha, Beta, Gamma, Delta, and Omicron variants, have emerged, lowering the protection rate of vaccines and even resulting in breakthrough infections. Additionally, some rare but severe adverse reactions induced by COVID-19 vaccines may raise safety concerns and hinder vaccine promotion; however, clinical studies have shown that the benefits of vaccination outweigh the risks caused by adverse reactions. Current vaccines approved with emergency use authorization (EUA) were originally adaptive for adults only, and infants, children, and adolescents are not included. New-generation vaccines are needed to overcome the challenges of limited adaptive age population, breakthrough infection (mainly due to virus variant emergencies), and critical adverse reactions. Fortunately, some advances in COVID-19 vaccines have been obtained regarding enlarged adaptive populations for clinical applications, such as the Pfizer/BioNTech vaccine and the Moderna vaccine. In this article, we provide a review on the challenges and recent advancements in COVID-19 vaccines. The development of next-generation COVID-19 vaccines should lay emphasis on the expansion of adaptive age populations in all individuals, the induction of immune responses to viral variants, the avoidance or alleviation of rare but potentially critical adverse reactions, and the discovery of subunit vaccines with adjuvants encapsulated in nanoparticles. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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13 pages, 1753 KiB

Open AccessReview

Phage-Derived Depolymerase: Its Possible Role for Secondary Bacterial Infections in COVID-19 Patients

by Amina Nazir, Jiaoyang Song, Yibao Chen and Yuqing Liu

Microorganisms 2023, 11(2), 424; https://doi.org/10.3390/microorganisms11020424 - 7 Feb 2023

Cited by 8 | Viewed by 2701

Abstract

As of 29 July 2022, there had been a cumulative 572,239,451 confirmed cases of COVID-19 worldwide, including 6,390,401 fatalities. COVID-19 patients with severe symptoms are usually treated with a combination of virus- and drug-induced immuno-suppression medicines. Critical clinical complications of the respiratory system [...] Read more.

As of 29 July 2022, there had been a cumulative 572,239,451 confirmed cases of COVID-19 worldwide, including 6,390,401 fatalities. COVID-19 patients with severe symptoms are usually treated with a combination of virus- and drug-induced immuno-suppression medicines. Critical clinical complications of the respiratory system due to secondary bacterial infections (SBIs) could be the reason for the high mortality rate in COVID-19 patients. Unfortunately, antimicrobial resistance is increasing daily, and only a few options are available in our antimicrobial armory. Hence, alternative therapeutic options such as enzymes derived from bacteriophages can be considered for treating SBIs in COVID-19 patients. In particular, phage-derived depolymerases have high antivirulent potency that can efficiently degrade bacterial capsular polysaccharides, lipopolysaccharides, and exopolysaccharides. They have emerged as a promising class of new antibiotics and their therapeutic role for bacterial infections is already confirmed in animal models. This review provides an overview of the rising incidence of SBIs among COVID-19 patients. We present a practicable novel workflow for phage-derived depolymerases that can easily be adapted for treating SBIs in COVID-19 patients. Full article

(This article belongs to the Special Issue SARS-CoV-2/COVID-19: Infection Models, Therapeutics and Vaccines)

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