Challenges and Progress in Vaccine Development for COVID-19 Coronavirus (SARS-CoV-2): A Review

Coronavirus Infectious Disease (COVID-19) has taken heavy toll on human lives and world economy across the globe. Till date, there is no specific treatment and pathological effects in COVID-19 are continuously evolving. The governments and authorities have announced various measures for personal care with use of face masks, physical distancing and prohibition of mass gatherings. These measures have certainly helped to contain the disease but with substantial economic slowdown. Thus mass immunization by vaccination is the top priority. With knowledge of MERS-SARS (Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome) in hand, researchers are rushing to vaccine development against SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) with newer technological platforms. However, the challenge lies in proving safety, quality and efficacy of vaccine with its resilience to manufacture it in large scales within stipulated time frame. The time consuming nature of classical phased clinical trials are substituted by human volunteer challenge with vaccination of humans engaging undertrial vaccine. This review discusses about various technology platforms being used and tried, their types and challenges in development of vaccine for SARS-CoV-2. Briefly, Indian perspective is also discussed in the race of vaccine development.

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COVID-19 Basics and Vaccine Development with a Canadian Perspective

Canadian Journal of Microbiology ◽

10.1139/cjm-2020-0421 ◽

2020 ◽

Author(s):

Marina Liu ◽

Xiongbiao Chen

Keyword(s):

Animal Models ◽

Severe Acute Respiratory Syndrome ◽

Clinical Evaluation ◽

Vaccine Development ◽

Specific Treatment ◽

Vaccine Candidates ◽

Preclinical Evaluation ◽

Canadian Perspective ◽

Basic Biology

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of July 31, 2020, there are at least 139 vaccine candidates from around the globe are in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada.

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Broad-Spectrum Antiviral Strategies and Nucleoside Analogues

Viruses ◽

10.3390/v13040667 ◽

2021 ◽

Vol 13 (4) ◽

pp. 667

Author(s):

Robert J. Geraghty ◽

Matthew T. Aliota ◽

Laurent F. Bonnac

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Broad Spectrum ◽

Vaccine Development ◽

Fast Response ◽

Mechanisms Of Action ◽

Public Health Emergency ◽

Nucleoside Analogues ◽

The Family ◽

Antiviral Nucleoside

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.

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Review of COVID-19 mRNA Vaccines: BNT162b2 and mRNA-1273

Journal of Pharmacy Practice ◽

10.1177/08971900211009650 ◽

2021 ◽

pp. 089719002110096

Author(s):

Shyh Poh Teo

Keyword(s):

Vaccine Development ◽

Safety Data ◽

The United States ◽

Virus Infections ◽

Phase 3 ◽

Vaccination Programs ◽

Safety Surveillance ◽

Mass Immunization ◽

United States Food ◽

States Food

The United States Food and Drug Administration recently issued emergency use authorization for 2 mRNA vaccines for preventing COVID-19 disease caused by SARS-CoV-2 virus infections. BNT162b2 from Pfizer-BioNTech and mRNA-1273 by Moderna are planned for use in mass-immunization programs to curb the pandemic. A brief overview of COVID-19 mRNA vaccines is provided, describing the SARS-CoV-2 RNA, how mRNA vaccines work and the advantages of mRNA over other vaccine platforms. The Pfizer-BioNTech collaboration journey to short-list mRNA vaccine candidates and finally selecting BNT162b2 based on safety data is outlined, followed by the Phase 3 study of BNT162b2 demonstrating 95% efficacy in preventing COVID-19 infections. Studies regarding mRNA-1273 (Moderna) are described, including extended immunogenicity data up to 119 days. The Phase 3 COVE study of mRNA-1273 eventually showed vaccine efficacy of 94.5%. Recommendations for future mRNA vaccine development are provided, including ongoing safety surveillance, evaluation in under-represented groups in previous studies and improving mRNA vaccine thermostability. Finally, further logistical considerations are required for manufacturing, storing, distribution and implementing mass vaccination programs to curb the pandemic.

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Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants

10.21203/rs.3.rs-400230/v1 ◽

2021 ◽

Author(s):

Satoshi Ikegame ◽

Mohammed Siddiquey ◽

Chuan-Tien Hung ◽

Griffin Haas ◽

Luca Brambilla ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Cell Line ◽

Vesicular Stomatitis Virus ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

The Novel ◽

Serum Samples ◽

Egfp Reporter ◽

Vesicular Stomatitis ◽

Reduced Activity

Abstract The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China1,2. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales have prompted re-evaluation of strategies to achieve universal vaccination3. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic4–8. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.

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Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

Vaccines ◽

10.3390/vaccines7040164 ◽

2019 ◽

Vol 7 (4) ◽

pp. 164 ◽

Cited By ~ 1

Author(s):

Julia Dubois ◽

Andrés Pizzorno ◽

Marie-Hélène Cavanagh ◽

Blandine Padey ◽

Claire Nicolas de Lamballerie ◽

...

Keyword(s):

Vaccine Development ◽

Specific Treatment ◽

Respiratory Pathogen ◽

Recombinant Viruses ◽

Human Airway Epithelium ◽

A Cell ◽

Strain Dependent ◽

Selection Of

Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75. The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system.

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Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach

Briefings in Bioinformatics ◽

10.1093/bib/bbaa340 ◽

2020 ◽

Author(s):

Aftab Alam ◽

Arbaaz Khan ◽

Nikhat Imam ◽

Mohd Faizan Siddiqui ◽

Mohd Waseem ◽

...

Keyword(s):

T Cell ◽

Vaccine Development ◽

Peptide Vaccine ◽

Specific Treatment ◽

T Cell Response ◽

Surface Glycoprotein ◽

Antigenic Peptides ◽

Population Coverage ◽

Geographical Regions ◽

Cluster Of Differentiation

Abstract The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

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Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.69.4.635-664.2005 ◽

2005 ◽

Vol 69 (4) ◽

pp. 635-664 ◽

Cited By ~ 449

Author(s):

Susan R. Weiss ◽

Sonia Navas-Martin

Keyword(s):

Animal Models ◽

Severe Acute Respiratory Syndrome ◽

Reverse Genetics ◽

Vaccine Development ◽

Hepatitis Virus ◽

Emerging Pathogen ◽

Murine Hepatitis Virus ◽

Veterinary Importance ◽

Positive Strand Rna ◽

Human Viruses

SUMMARY Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.

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Oral vaccines for finfish: academic theory or commercial reality?

Animal Health Research Reviews ◽

10.1079/ahr200488 ◽

2004 ◽

Vol 5 (2) ◽

pp. 301-304 ◽

Cited By ~ 35

Author(s):

Grant W. Vandenberg

Keyword(s):

Immune Response ◽

Oral Delivery ◽

Vaccine Development ◽

Resistant Bacteria ◽

Oral Vaccines ◽

Growth Depression ◽

Antibiotic Resistant ◽

Protective Antigens ◽

Mass Immunization ◽

Duration Of Protection

AbstractAquaculture is the fastest growing food-producing sector, providing an acceptable supplement to and substitute for wild fish and plants. Increased production intensification, particularly in high-value species, involves substantial stress, which, as in other captive livestock species, has resulted in outbreaks of major diseases and related mortalities. Widespread use of antibiotics has led to the development of antibiotic-resistant bacteria and the accumulation of antibiotics in the environment and the flesh of fish. Thus, recently effort has been dedicated to vaccine development. Vaccination in fish is complicated by their aquatic environment. Individual injections are labor-intensive and stressful, since fish have to be removed from the water and anaesthetized. Some vaccines offer a limited duration of protection, and thus booster applications are required. In salmonid species, many commercial vaccines use oil-based adjuvants, resulting in a greatly improved duration of protection. However, oil-based adjuvants have been related to significant growth depression, internal adhesions and injection site melanization, resulting in carcass downgrading. Oral administration to aquatic species is by far the most appealing method of vaccine delivery: there is no handling of the fish, which reduces stress; and administration is easy and suitable for mass immunization. However, few oral vaccines have been commercialized, due in part to the increased quantity of antigen required to provoke an immune response, and the lack of an adequate duration of protection. For effective oral delivery, protective antigens must avoid digestive hydrolysis and be taken up in the hindgut in order to induce an effective protective immune response. Antigen encapsulation technologies have been used to protect antigen; however, such strategies can be expensive and are not always effective. Alternative approaches, currently under development, are discussed.

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Identification and analysis of novel variants in SARS-COV-2 genomes isolated from the Kingdom of Bahrain

10.1101/2021.01.25.428191 ◽

2021 ◽

Author(s):

Khalid M bindayna ◽

Abdel Halim Deifalla ◽

Hicham Ezzat Mohammed Mokbel

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Phylogenetic Tree ◽

Vaccine Development ◽

High Impact ◽

Modern World ◽

Multiple Origins ◽

Novel Variants ◽

Economic Needs ◽

Origin Analysis

AbstractThe challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccine’s availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SERS-CoV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SERS-CoV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrain’s SERS-CoV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-CoV2. Our research could have a high impact on vaccine development and distinguishes the source of SERS-CoV2 in the Kingdom of Bahrain.

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SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

Frontiers in Immunology ◽

10.3389/fimmu.2021.701501 ◽

2021 ◽

Vol 12 ◽

Author(s):

Daniel Martínez-Flores ◽

Jesús Zepeda-Cervantes ◽

Adolfo Cruz-Reséndiz ◽

Sergio Aguirre-Sampieri ◽

Alicia Sampieri ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Clinical Manifestations ◽

Receptor Binding Domain ◽

Current Vaccine ◽

Main Target ◽

Different Types ◽

Antigenic Domains

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.

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