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

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

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 156205

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Guest Editor
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
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Special Issue Information

Dear Colleagues,

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. Currently, the world is concerned about the 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 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

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Keywords

  • Vaccine
  • SARS-CoV-2
  • COVID-19
  • Antibodies
  • Antivirals

Published Papers (20 papers)

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Research

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11 pages, 951 KiB  
Article
Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19
by Jiao Tong, Chenxi Zhu, Hanyu Lai, Chunchao Feng and Dapeng Zhou
Vaccines 2021, 9(3), 296; https://doi.org/10.3390/vaccines9030296 - 22 Mar 2021
Cited by 7 | Viewed by 3404
Abstract
The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day [...] Read more.
The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 μg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries. Full article
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17 pages, 2826 KiB  
Article
Localized and Systemic Immune Responses against SARS-CoV-2 Following Mucosal Immunization
by Shaswath S. Chandrasekar, Yashdeep Phanse, Rachel E. Hildebrand, Mostafa Hanafy, Chia-Wei Wu, Chungyi H. Hansen, Jorge E. Osorio, M. Suresh and Adel M. Talaat
Vaccines 2021, 9(2), 132; https://doi.org/10.3390/vaccines9020132 - 06 Feb 2021
Cited by 27 | Viewed by 6751
Abstract
The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when [...] Read more.
The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when used against avian coronavirus. Here, we report on the immune responses elicited by mucosal homologous plasmid and a heterologous immunization strategy using a plasmid vaccine and a Modified Vaccinia Ankara (MVA) expressing SARS-CoV-2 spike (S) and nucleocapsid (N) antigens. Only the heterologous intranasal immunization strategy elicited neutralizing antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice, suggesting a protective vaccine. The same prime/boost strategy led to the induction of type 1 and type 17 T-cell responses and polyfunctional T-cells expressing multiple type 1 cytokines (e.g., IFN-γ, TNFα, IL-2) in the lungs and spleens of vaccinated mice. In contrast, the plasmid homologous vaccine strategy led to the induction of local mono and polyfunctional T-cells secreting IFN-γ. Outcomes of this study support the potential of QAC-nano vaccines to elicit significant mucosal immune responses against respiratory coronaviruses. Full article
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10 pages, 2091 KiB  
Communication
Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome
by Iwona Karwaciak, Anna Sałkowska, Kaja Karaś, Jarosław Dastych and Marcin Ratajewski
Vaccines 2021, 9(1), 54; https://doi.org/10.3390/vaccines9010054 - 15 Jan 2021
Cited by 40 | Viewed by 8132
Abstract
The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic [...] Read more.
The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact with the virus or its components, or how immune homeostasis becomes disrupted, leading to the rapid deterioration of a patient’s condition. In the present work, we show that SARS-CoV-2 proteins induce the expression and secretion of IL-6 by human monocytes and macrophages, the first line cells of antiviral immune responses. IL-6 may play a negative role in the course of COVID-19 by inhibiting Th1-dependent immunity and stimulating Th17 lymphocytes, thus leading to an increased probability of a cytokine storm. Full article
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8 pages, 699 KiB  
Article
Flattening the Curve of COVID-19 Vaccine Rejection—An International Overview
by Wojciech Feleszko, Piotr Lewulis, Adam Czarnecki and Paweł Waszkiewicz
Vaccines 2021, 9(1), 44; https://doi.org/10.3390/vaccines9010044 - 13 Jan 2021
Cited by 89 | Viewed by 12464
Abstract
Background: If globally implemented, a safe coronavirus disease 2019 (COVID-19) vaccination program will have broad clinical and socioeconomic benefits. However, individuals who anticipate that the coronavirus vaccine will bring life back to normality may be disappointed, due to the emerging antivaccination attitude within [...] Read more.
Background: If globally implemented, a safe coronavirus disease 2019 (COVID-19) vaccination program will have broad clinical and socioeconomic benefits. However, individuals who anticipate that the coronavirus vaccine will bring life back to normality may be disappointed, due to the emerging antivaccination attitude within the general population. Methods: We surveyed a sample of adult Polish citizens (n = 1066), and compared it with the data on international COVID-19 vaccine reluctance. Results: In 20 national surveys, the vaccine averseness for the anticipated COVID-19 vaccine varied from meager (2–6% China) to very high (43%, Czech Republic, and 44%, Turkey) and in most countries was much higher than regular vaccination reluctance, which varies between 3% (Egypt) and 55% (Russia). Conclusions: These results suggest that a 67% herd immunity may be possible only if mandatory preventive vaccination programs start early and are combined with coordinated education efforts supported by legislative power and social campaigns. Full article
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10 pages, 634 KiB  
Article
Impact of Recommended Maternal Vaccination Programs on the Clinical Presentation of SARS-CoV-2 Infection: A Prospective Observational Study
by Maria Luisa de la Cruz Conty, Maria Begoña Encinas Pardilla, Marta Garcia Sanchez, Laura Gonzalez Rodriguez, Marta Luisa Muner-Hernando, Ana Royuela Vicente, Pilar Pintado Recarte, Alicia Martinez Varea, Clara Martinez Diago, Sara Cruz Melguizo, Oscar Martinez-Perez and on behalf of the Spanish Obstetric Emergency Group
Vaccines 2021, 9(1), 31; https://doi.org/10.3390/vaccines9010031 - 08 Jan 2021
Cited by 9 | Viewed by 3396
Abstract
The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine [...] Read more.
The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign. Full article
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14 pages, 4424 KiB  
Communication
COVID-19 Infection Detection and Prevention by SARS-CoV-2 Active Antigens: A Synthetic Vaccine Approach
by José Manuel Lozano, Luz Mary Salazar, Ángela Torres, Adriana Arévalo-Jamaica, Carlos Franco-Muñoz, Marcela Mercado-Reyes and Fabio Ancizar Aristizabal
Vaccines 2020, 8(4), 692; https://doi.org/10.3390/vaccines8040692 - 18 Nov 2020
Cited by 3 | Viewed by 3687
Abstract
COVID-19, a global pandemic causing to date more than 50 million cases and more than a million deaths, has to be controlled. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was identified as the causative agent. Controversy about this virus origin and infectious mechanism [...] Read more.
COVID-19, a global pandemic causing to date more than 50 million cases and more than a million deaths, has to be controlled. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was identified as the causative agent. Controversy about this virus origin and infectious mechanism for adapting to humans remains a matter for discussion. Among all strategies for obtaining safe and potent vaccines, approaches based on attenuated-killed virus and non-replicating RNA viral vectors are demonstrating promising results. However, specificity of viral components targeted by human antibodies so far has not been demonstrated. A consistent strategy for obtaining functional-active antigens from SARS-CoV-2 specific ligands lead us to propose and test a number of synthetic components. From hundreds of starting sequences only fifteen fulfilled the design requirements and were produced as monomer and polymer forms and immuno-chemically tested. The design was based on worldwide representative reported virus genomes. A bioinformatics scheme by conventional methods and knowledge on MHC-I and II antigen processing mechanisms and HLA haplotype-restriction was performed including sensitive and resistant human populations to virus infection. Covid-19 patients’ sera reactivity for synthetic SARS-CoV-2-designed components have proven a high recognition of specific molecules, as well as some evidence for a long-lasting humoral immune response. Full article
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10 pages, 6927 KiB  
Communication
SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors
by Anna Sałkowska, Iwona Karwaciak, Kaja Karaś, Jarosław Dastych and Marcin Ratajewski
Vaccines 2020, 8(4), 673; https://doi.org/10.3390/vaccines8040673 - 12 Nov 2020
Cited by 13 | Viewed by 3015
Abstract
The outbreak of the SARS-CoV-2 virus in December 2019 has caused the deaths of several hundred thousand people worldwide. Currently, the pathogenesis of COVID-19 is poorly understood. During the course of COVID-19 infection, many patients experience deterioration, which might be associated with systemic [...] Read more.
The outbreak of the SARS-CoV-2 virus in December 2019 has caused the deaths of several hundred thousand people worldwide. Currently, the pathogenesis of COVID-19 is poorly understood. During the course of COVID-19 infection, many patients experience deterioration, which might be associated with systemic inflammation and cytokine storm syndrome; however, other patients have mild symptoms or are asymptomatic. There are some suggestions that impaired cellular immunity through a reduction in Th1 response and IFNG (interferon gamma) expression, as well as cross-reactivity with common cold coronaviruses, might be involved in the differential COVID-19 course. Here, we show that CD4+ cells isolated from unexposed healthy donors that were differentiated towards the Th1 lineage in the presence of SARS-CoV-2 proteins exhibited induction of IFNG. Interestingly, the same cells induced to differentiate towards a Th17 lineage did not exhibit changes in IFNG expression or Th17-related cytokines. This suggests the cellular response to SARS-CoV-2 viral proteins is primarily associated with Th1 lymphocytes and may be dependent on past infections with common cold coronaviruses or vaccinations that induce unspecific cellular responses, e.g., BCG (Bacillus Calmette-Guérin). Thus, our results might explain the high variability in the course of COVID-19 among populations of different countries. Full article
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20 pages, 4532 KiB  
Article
Possible Cross-Reactivity between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death
by Robert Root-Bernstein
Vaccines 2020, 8(4), 559; https://doi.org/10.3390/vaccines8040559 - 24 Sep 2020
Cited by 27 | Viewed by 7082
Abstract
Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. [...] Read more.
Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to cross-reacting material CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Haemophilus influenzae type b (Hib) and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable. Full article
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17 pages, 4869 KiB  
Article
Vaccine Design from the Ensemble of Surface Glycoprotein Epitopes of SARS-CoV-2: An Immunoinformatics Approach
by Noor Rahman, Fawad Ali, Zarrin Basharat, Muhammad Shehroz, Muhammad Kazim Khan, Philippe Jeandet, Eugenie Nepovimova, Kamil Kuca and Haroon Khan
Vaccines 2020, 8(3), 423; https://doi.org/10.3390/vaccines8030423 - 28 Jul 2020
Cited by 53 | Viewed by 7372
Abstract
The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL [...] Read more.
The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. From the overlapped epitopes, we designed five vaccine constructs C1–C5. Based on antigenicity, allergenicity, solubility, different physiochemical properties, and molecular docking scores, we selected the vaccine construct 1 (C1) for further processing. Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of −43.48, −65.88, and −60.24 Kcal/mol, respectively. The docked complex was further simulated, which revealed that both molecules remain stable with minimum RMSF. Activation of TLRs induces downstream pathways to produce pro-inflammatory cytokines against viruses and immune system simulation shows enhanced antibody production after the booster dose. In conclusion, C1 was the best vaccine candidate among all designed constructs to elicit an immune response SARS-CoV-2 and combat the coronavirus disease (COVID-19). Full article
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15 pages, 1663 KiB  
Article
Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design
by Dongliang Wang, Jinhui Mai, Wenfeng Zhou, Wanting Yu, Yang Zhan, Naidong Wang, Neal D. Epstein and Yi Yang
Vaccines 2020, 8(3), 355; https://doi.org/10.3390/vaccines8030355 - 03 Jul 2020
Cited by 50 | Viewed by 7713
Abstract
Currently, there is limited knowledge about the immunological profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We used computer-based immunoinformatic analysis and the newly resolved 3-dimensional (3D) structures of the SARS-CoV-2 S trimeric protein, together with analyses of the immunogenic profiles of [...] Read more.
Currently, there is limited knowledge about the immunological profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We used computer-based immunoinformatic analysis and the newly resolved 3-dimensional (3D) structures of the SARS-CoV-2 S trimeric protein, together with analyses of the immunogenic profiles of SARS-CoV, to anticipate potential B-cell and T-cell epitopes of the SARS-CoV-2 S protein for vaccine design, particularly for peptide-driven vaccine design and serological diagnosis. Nine conserved linear B-cell epitopes and multiple discontinuous B-cell epitopes composed of 69 residues on the surface of the SARS-CoV-2 trimeric S protein were predicted to be highly antigenic. We found that the SARS-CoV-2 S protein has a different antigenic profile than that of the SARS-CoV S protein due to the variations in their primary and 3D structures. Importantly, SARS-CoV-2 may exploit an immune evasion mechanism through two point mutations in the critical and conserved linear neutralization epitope (overlap with fusion peptide) around a sparsely glycosylated area. These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein. In addition, 62 T-cell epitopes in the SARS-CoV-2 S protein were predicted in our study. The structure-based immunoinformatic analysis for the SARS-CoV-2 S protein in this study may improve vaccine design, diagnosis, and immunotherapy against the pandemic of COVID-19. Full article
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Review

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16 pages, 1610 KiB  
Review
SARS-CoV-2 Genetic Variability and Non-Specific Immunity Associated with the Use of Different BCG Strains—A Molecular and Clinical Approach
by Jakub Kulus, Magdalena Kulus, Katarzyna Stefańska, Jarosław Sobolewski, Hanna Piotrowska-Kempisty, Paul Mozdziak and Bartosz Kempisty
Vaccines 2021, 9(6), 639; https://doi.org/10.3390/vaccines9060639 - 10 Jun 2021
Cited by 3 | Viewed by 3549
Abstract
The effect of BCG vaccination against tuberculosis on the reduction in COVID-19 infection is related to the effect of the BCG vaccine on the immunomodulation of non-specific immunity. In the early stages of the pandemic, countries with universal BCG vaccination programs registered a [...] Read more.
The effect of BCG vaccination against tuberculosis on the reduction in COVID-19 infection is related to the effect of the BCG vaccine on the immunomodulation of non-specific immunity. In the early stages of the pandemic, countries with universal BCG vaccination programs registered a low number of new cases of COVID-19, with the situation now reversed, as exemplified by India. The high genetic variability of SARS-CoV-2, a known characteristic of RNA viruses, causing the occurrence of SARS-CoV-2 variants may have led to the virus adapting to overcome the initial immune protection. The strains from the United Kingdom (B1.1.7), Brazil (B1.1.28 and B1.1.33), South Africa (B.1.351), and India (B.1.617) are characterized by a greater ability to spread in the environment, in comparison with the original infectious agent of SARS-CoV-2. It should be remembered that the large variation in the genetic makeup of SARS-CoV-2 may result in future changes in its pathogenicity, immunogenicity and antigenicity, and therefore it is necessary to carefully study the mutations occurring within the virus to determine whether the current vaccines will remain effective. However, most studies show that monoclonal antibodies produced after vaccination against COVID-19 are effective against the newly developed variants. Full article
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23 pages, 9502 KiB  
Review
Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm
by Ali A. Rabaan, Shamsah H. Al-Ahmed, Javed Muhammad, Amjad Khan, Anupam A Sule, Raghavendra Tirupathi, Abbas Al Mutair, Saad Alhumaid, Awad Al-Omari, Manish Dhawan, Ruchi Tiwari, Khan Sharun, Ranjan K. Mohapatra, Saikat Mitra, Muhammad Bilal, Salem A. Alyami, Talha Bin Emran, Mohammad Ali Moni and Kuldeep Dhama
Vaccines 2021, 9(5), 436; https://doi.org/10.3390/vaccines9050436 - 29 Apr 2021
Cited by 150 | Viewed by 16718
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications. Full article
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22 pages, 4197 KiB  
Review
An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times
by Cielo García-Montero, Oscar Fraile-Martínez, Coral Bravo, Diego Torres-Carranza, Lara Sanchez-Trujillo, Ana M. Gómez-Lahoz, Luis G. Guijarro, Natalio García-Honduvilla, Angel Asúnsolo, Julia Bujan, Jorge Monserrat, Encarnación Serrano, Melchor Álvarez-Mon, Juan A De León-Luis, Miguel A. Álvarez-Mon and Miguel A. Ortega
Vaccines 2021, 9(5), 433; https://doi.org/10.3390/vaccines9050433 - 27 Apr 2021
Cited by 77 | Viewed by 12067
Abstract
Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step [...] Read more.
Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac). Full article
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16 pages, 1170 KiB  
Review
COVID-19 Vaccines Currently under Preclinical and Clinical Studies, and Associated Antiviral Immune Response
by Swati Jain, Himanshu Batra, Poonam Yadav and Subhash Chand
Vaccines 2020, 8(4), 649; https://doi.org/10.3390/vaccines8040649 - 03 Nov 2020
Cited by 43 | Viewed by 15566
Abstract
With a death toll of over one million worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has become the most devastating humanitarian catastrophe in recent decades. The fear of acquiring infection and spreading to vulnerable people has severely impacted society’s socio-economic status. To put [...] Read more.
With a death toll of over one million worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has become the most devastating humanitarian catastrophe in recent decades. The fear of acquiring infection and spreading to vulnerable people has severely impacted society’s socio-economic status. To put an end to this growing number of infections and deaths as well as to switch from restricted to everyday living, an effective vaccine is desperately needed. As a result, enormous efforts have been made globally to develop numerous vaccine candidates in a matter of months. Currently, over 30 vaccine candidates are under assessment in clinical trials, with several undergoing preclinical studies. Here, we reviewed the major vaccine candidates based on the specific vaccine platform utilized to develop them. We also discussed the immune responses generated by these candidates in humans and preclinical models to determine vaccine safety, immunogenicity, and efficacy. Finally, immune responses induced in recovered COVID-19 patients and their possible vaccine development implications were also briefly reviewed. Full article
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44 pages, 6971 KiB  
Review
Current Clinical Trials Protocols and the Global Effort for Immunization against SARS-CoV-2
by Gabriel N. A. Rego, Mariana P. Nucci, Arielly H. Alves, Fernando A. Oliveira, Luciana C. Marti, Leopoldo P. Nucci, Javier B. Mamani and Lionel F. Gamarra
Vaccines 2020, 8(3), 474; https://doi.org/10.3390/vaccines8030474 - 25 Aug 2020
Cited by 32 | Viewed by 13246
Abstract
Coronavirus disease 2019 (COVID-19) is the biggest health challenge of the 21st century, affecting millions of people globally. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ignited an unprecedented effort from the scientific community in the development of new vaccines [...] Read more.
Coronavirus disease 2019 (COVID-19) is the biggest health challenge of the 21st century, affecting millions of people globally. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ignited an unprecedented effort from the scientific community in the development of new vaccines on different platforms due to the absence of a broad and effective treatment for COVID-19 or prevention strategy for SARS-CoV-2 dissemination. Based on 50 current studies selected from the main clinical trial databases, this systematic review summarizes the global race for vaccine development against COVID-19. For each study, the main intervention characteristics, the design used, and the local or global center partnerships created are highlighted. Most vaccine developments have taken place in Asia, using a viral vector method. Two purified inactivated SARS-CoV-2 vaccine candidates, an mRNA-based vaccine mRNA1273, and the chimpanzee adenoviral vaccine ChAdOx1 are currently in phase III clinical trials in the respective countries Brazil, the United Arab Emirates, the USA, and the United Kingdom. These vaccines are being developed based on a quickly formed network of collaboration. Full article
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21 pages, 282 KiB  
Review
Vaccines against Coronaviruses: The State of the Art
by Cristiano Conte, Francesco Sogni, Paola Affanni, Licia Veronesi, Alberto Argentiero and Susanna Esposito
Vaccines 2020, 8(2), 309; https://doi.org/10.3390/vaccines8020309 - 17 Jun 2020
Cited by 43 | Viewed by 7865
Abstract
The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments [...] Read more.
The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus. Full article

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4 pages, 194 KiB  
Viewpoint
Why It Is Important to Develop an Effective and Safe Pediatric COVID-19 Vaccine
by Nicola Principi and Susanna Esposito
Vaccines 2021, 9(2), 127; https://doi.org/10.3390/vaccines9020127 - 05 Feb 2021
Cited by 19 | Viewed by 4560
Abstract
The need to cope with the medical, social, and economic storm due to the new coronavirus 2019 (COVID-19) pandemic as quickly as possible has led to the very rapid development of a huge number of vaccines. All these vaccines have been mainly developed [...] Read more.
The need to cope with the medical, social, and economic storm due to the new coronavirus 2019 (COVID-19) pandemic as quickly as possible has led to the very rapid development of a huge number of vaccines. All these vaccines have been mainly developed in healthy adults and, in some cases, in the elderly. Children were marginally involved as, according to the clinical trial registry Clinical Trials.gov, only very few studies have included children among subjects to enroll, although just a few weeks after the pandemic declaration, the US Food and Drug Administration had highlighted the importance of vaccine evaluation in pediatrics. Availability of an effective and safe pediatric COVID-19 vaccine appears mandatory for several clinical and epidemiological reasons. However, as the development of an effective and safe pediatric vaccine seems far from easy, strong cooperation among governments, researchers, and pharmaceutical companies is highly desirable. Full article
9 pages, 250 KiB  
Perspective
The Strange Case of BCG and COVID-19: The Verdict Is Still up in the Air
by Radha Gopalaswamy, Natarajan Ganesan, Kalamani Velmurugan, Vivekanandhan Aravindhan and Selvakumar Subbian
Vaccines 2020, 8(4), 612; https://doi.org/10.3390/vaccines8040612 - 16 Oct 2020
Cited by 8 | Viewed by 3533
Abstract
COVID-19, caused by a novel coronavirus, SARS-CoV-2, contributes significantly to the morbidity and mortality in humans worldwide. In the absence of specific vaccines or therapeutics available, COVID-19 cases are managed empirically with the passive immunity approach and repurposing of drugs used for other [...] Read more.
COVID-19, caused by a novel coronavirus, SARS-CoV-2, contributes significantly to the morbidity and mortality in humans worldwide. In the absence of specific vaccines or therapeutics available, COVID-19 cases are managed empirically with the passive immunity approach and repurposing of drugs used for other conditions. Recently, a concept that bacilli Calmette–Guerin (BCG) vaccination could confer protection against COVID-19 has emerged. The foundation for this widespread attention came from several recent articles, including the one by Miller et al. submitted to MedRxiv, a pre-print server. The authors of this article suggest that a correlation exists between countries with a prolonged national BCG vaccination program and the morbidity/mortality due to COVID-19. Further, clinical BCG vaccination trials are currently ongoing in the Netherlands, Australia, the UK, and Germany with the hope of reducing mortality due to COVID-19. Although BCG vaccination helps protect children against tuberculosis, experimental studies have shown that BCG can also elicit a non-specific immune response against viral and non-mycobacterial infections. Here, we summarize the pros and cons of BCG vaccination and critically analyze the evidence provided for the protective effect of BCG against COVID-19 and highlight the confounding factors in these studies. Full article
10 pages, 532 KiB  
Brief Report
Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2
by Mariangela Garofalo, Monika Staniszewska, Stefano Salmaso, Paolo Caliceti, Katarzyna Wanda Pancer, Magdalena Wieczorek and Lukasz Kuryk
Vaccines 2020, 8(2), 293; https://doi.org/10.3390/vaccines8020293 - 10 Jun 2020
Cited by 11 | Viewed by 6086
Abstract
The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations [...] Read more.
The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency. Full article
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8 pages, 2019 KiB  
Brief Report
A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity?
by Sung-Jae Kim, Van-Giap Nguyen, Yong-Ho Park, Bong-Kyun Park and Hee-Chun Chung
Vaccines 2020, 8(2), 220; https://doi.org/10.3390/vaccines8020220 - 14 May 2020
Cited by 38 | Viewed by 6567
Abstract
The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes [...] Read more.
The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes. Full article
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