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1.
Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165

ABSTRACT

BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.


Subject(s)
Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
3.
Drug Deliv Transl Res ; 11(3): 748-787, 2021 06.
Article in English | MEDLINE | ID: covidwho-1343054

ABSTRACT

The host immune system is highly compromised in case of viral infections and relapses are very common. The capacity of the virus to destroy the host cell by liberating its own DNA or RNA and replicating inside the host cell poses challenges in the development of antiviral therapeutics. In recent years, many new technologies have been explored for diagnosis, prevention, and treatment of viral infections. Nanotechnology has emerged as one of the most promising technologies on account of its ability to deal with viral diseases in an effective manner, addressing the limitations of traditional antiviral medicines. It has not only helped us to overcome problems related to solubility and toxicity of drugs, but also imparted unique properties to drugs, which in turn has increased their potency and selectivity toward viral cells against the host cells. The initial part of the paper focuses on some important proteins of influenza, Ebola, HIV, herpes, Zika, dengue, and corona virus and those of the host cells important for their entry and replication into the host cells. This is followed by different types of nanomaterials which have served as delivery vehicles for the antiviral drugs. It includes various lipid-based, polymer-based, lipid-polymer hybrid-based, carbon-based, inorganic metal-based, surface-modified, and stimuli-sensitive nanomaterials and their application in antiviral therapeutics. The authors also highlight newer promising treatment approaches like nanotraps, nanorobots, nanobubbles, nanofibers, nanodiamonds, nanovaccines, and mathematical modeling for the future. The paper has been updated with the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19.Graphical abstract.


Subject(s)
Antiviral Agents/administration & dosage , Drug Carriers , Nanomedicine , Nanoparticles , Polymers/chemistry , Vaccination , Viral Vaccines/administration & dosage , Virus Diseases/prevention & control , Antiviral Agents/chemistry , COVID-19 Vaccines/administration & dosage , Drug Compounding , Humans , Viral Vaccines/chemistry , Virus Diseases/immunology , Virus Diseases/virology
4.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288899

ABSTRACT

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Subject(s)
Antiviral Agents/chemistry , Drug Carriers/chemistry , Nanomedicine , Respiratory Tract Infections/pathology , Viral Vaccines/chemistry , Virus Diseases/pathology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Immune System/metabolism , Respiratory Tract Infections/therapy , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Virus Diseases/immunology , Virus Diseases/prevention & control , Virus Diseases/therapy
5.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266401

ABSTRACT

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.


Subject(s)
COVID-19 Vaccines , Neoplasms/therapy , RNA, Messenger , SARS-CoV-2/immunology , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/therapeutic use , Drug Stability , Humans , Influenza, Human/epidemiology , Influenza, Human/immunology , Influenza, Human/prevention & control , Neoplasms/epidemiology , Neoplasms/immunology , Pandemics , RNA Stability/physiology , RNA, Messenger/administration & dosage , RNA, Messenger/adverse effects , RNA, Messenger/chemistry , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccination/methods , Viral Vaccines/adverse effects , Viral Vaccines/chemistry , Viral Vaccines/genetics
6.
J Inorg Biochem ; 219: 111454, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157503

ABSTRACT

In recent years, some viruses have caused a grave crisis to global public health, especially the human coronavirus. A truly effective vaccine is therefore urgently needed. Vaccines should generally have two features: delivering antigens and modulating immunity. Adjuvants have an unshakable position in the battle against the virus. In addition to the perennial use of aluminium adjuvant, nanoparticles have become the developing adjuvant candidates due to their unique properties. Here we introduce several typical nanoparticles and their antivirus vaccine adjuvant applications. Finally, for the combating of the coronavirus, we propose several design points, hoping to provide ideas for the development of personalized vaccines and adjuvants and accelerate the clinical application of adjuvants.


Subject(s)
Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Nanoparticles/chemistry , Viral Vaccines/immunology , Aluminum/chemistry , Antibodies, Neutralizing/drug effects , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Calcium Phosphates/chemistry , Chitosan/chemistry , Gold/chemistry , Humans , Nanoparticles/administration & dosage , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology , Viral Vaccines/chemistry
7.
Cell Host Microbe ; 29(3): 327-333, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1126778

ABSTRACT

Most viral vaccines are based on inducing neutralizing antibodies (NAbs) against the virus envelope or spike glycoproteins. Many viral surface proteins exist as trimers that transition from a pre-fusion state when key NAb epitopes are exposed to a post-fusion form in which the potential for virus-cell fusion no longer exists. For optimal vaccine performance, these viral proteins are often engineered to enhance stability and presentation of these NAb epitopes. The method involves the structure-guided introduction of proline residues at key positions that maintain the trimer in the pre-fusion configuration. We review how this technique emerged during HIV-1 Env vaccine development and its subsequent wider application to other viral vaccines including SARS-CoV-2.


Subject(s)
Proline/chemistry , Proline/immunology , Viral Vaccines/chemistry , Viral Vaccines/immunology , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Humans , Models, Molecular , Proline/genetics , Protein Engineering , Viral Vaccines/genetics
8.
mBio ; 12(2)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1115090

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the CoV disease 2019 (COVID-19) pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of an RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. Sixteen- to 20-month-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss, or clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious virus in nasal washes and lungs as well as of viral RNA in respiratory organs. This study demonstrates that spike RBD-nanoparticles are an effective protein vaccine candidate against SARS-CoV-2.


Subject(s)
COVID-19/prevention & control , Nanoparticles/chemistry , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Viral Vaccines/therapeutic use , Angiotensin-Converting Enzyme 2/chemistry , Animals , Cellulose/chemistry , Coronavirus/immunology , Coronavirus/pathogenicity , Ferrets , Ferritins , SARS-CoV-2/immunology , Viral Vaccines/chemistry
9.
J Control Release ; 330: 529-539, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-988295

ABSTRACT

The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.


Subject(s)
AIDS Vaccines/chemistry , COVID-19 Vaccines/chemistry , Immunity, Humoral/drug effects , Lipids/chemistry , Nanoparticles , Viral Vaccines/chemistry , AIDS Vaccines/administration & dosage , Adjuvants, Immunologic , Animals , Antigen Presentation , Antigen-Antibody Reactions , COVID-19 Vaccines/administration & dosage , Dendritic Cells/immunology , Dendritic Cells/metabolism , HIV-1 , Humans , Lymph Nodes/immunology , Mice , Mice, Inbred BALB C , Rabbits , SARS-CoV-2 , Viral Vaccines/administration & dosage
10.
J Proteome Res ; 19(11): 4649-4654, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-974860

ABSTRACT

The Bacillus Calmette-Guerin vaccine is still widely used in the developing world. The vaccination prevents infant death not only from tuberculosis but also from unrelated infectious agents, especially respiratory tract infections and neonatal sepsis. It is proposed that these off-target protective effects of the BCG vaccine are mediated by the general long-term boosting of innate immune mechanisms, also termed "trained innate immunity". Recent studies indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs and encourage the initiation of several clinical studies with the expectation that revaccination with BCG could reduce the incidence and severity of COVID-19. Here, presented results from the bioinformatics analysis of the Mycobacterium bovis (strain BCG/Pasteur 1173P2) proteome suggests four immunodominant antigens that could induce an immune response against SARS-CoV-2.


Subject(s)
BCG Vaccine , Bacterial Proteins , Betacoronavirus , Coronavirus Infections , Drug Repositioning , Pandemics , Pneumonia, Viral , BCG Vaccine/chemistry , BCG Vaccine/immunology , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Betacoronavirus/chemistry , Betacoronavirus/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Humans , Mycobacterium bovis/chemistry , Mycobacterium bovis/immunology , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Proteome/chemistry , Proteome/immunology , SARS-CoV-2 , Viral Vaccines/chemistry , Viral Vaccines/immunology
11.
Microbiol Immunol ; 65(4): 154-160, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-965526

ABSTRACT

Currently, the whole world is facing the coronavirus disease-19 pandemic. As of now, approximately 0.15 million people around the globe are infected with the novel coronavirus. In the last decade, two strains of the coronavirus family, severe acute respiratory syndrome-related coronavirus and Middle East respiratory syndrome coronavirus, also resulted in epidemics in south Asian and the Middle Eastern countries with high mortality rate. This scenario demands the development of a putative vaccine which may provide immunity against all current and new evolving coronavirus strains. In this study, we designed an epitope-based vaccine using an immunoinformatic approach. This vaccine may protect against all coronavirus strains. The vaccine is developed by considering the geographical distribution of coronavirus strains and host genetics (Chinese population). Nine experimentally validated epitopes sequences from coronavirus strains were used to derive the variants considering the conservancy in all strains. Further, the binding affinities of all derived variants were checked with most abundant human leukocyte antigen alleles in the Chinese population. Three major histocompatibility complex (MHC) Class I epitopes from spike glycoprotein and nucleoprotein showed sufficient binding while one MHC Class II epitope from spike glycoprotein was found to be an effective binder. A cocktail of these epitopes gave more than 95% population coverage in the Chinese population. Moreover, molecular dynamics simulation supported the aforementioned predictions. Further, in vivo studies are needed to confirm the immunogenic potential of these vaccines.


Subject(s)
Coronavirus Infections/prevention & control , Coronavirus/immunology , Viral Vaccines/immunology , Alleles , Amino Acid Sequence , China , Coronavirus/chemistry , Coronavirus/genetics , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , HLA Antigens/genetics , HLA Antigens/immunology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics
13.
Microb Pathog ; 149: 104560, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-857004

ABSTRACT

Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demonstrate little or no cross protection. In order to curb the menace of the disease therefore, broad based vaccines are urgently needed. The aim of this study was to develop a recombinant DNA vaccine candidate for improved protection of avian infectious bronchitis in poultry. Using bioinformatics and molecular cloning procedures, sets of monovalent and bivalent DNA vaccine constructs were developed based on the S1 glycoprotein from classical and variants IBV strains namely, M41 and CR88 respectively. The candidate vaccine was then encapsulated with a chitosan and saponin formulated nanoparticle for enhanced immunogenicity and protective capacity. RT-PCR assay and IFAT were used to confirm the transcriptional and translational expression of the encoded proteins respectively, while ELISA and Flow-cytometry were used to evaluate the immunogenicity of the candidate vaccine following immunization of various SPF chicken groups (A-F). Furthermore, histopathological changes and virus shedding were determined by quantitative realtime PCR assay and lesion scoring procedure respectively following challenge of various subgroups with respective wild-type IBV viruses. Results obtained from this study showed that, groups vaccinated with a bivalent DNA vaccine construct (pBudCR88-S1/M41-S1) had a significant increase in anti-IBV antibodies, CD3+ and CD8+ T-cells responses as compared to non-vaccinated groups. Likewise, the bivalent vaccine candidate significantly decreased the oropharyngeal and cloacal virus shedding (p < 0.05) compared to non-vaccinated control. Chickens immunized with the bivalent vaccine also exhibited milder clinical signs as well as low tracheal and kidney lesion scores following virus challenge when compared to control groups. Collectively, the present study demonstrated that bivalent DNA vaccine co-expressing dual S1 glycoprotein induced strong immune responses capable of protecting chickens against infection with both M41 and CR88 IBV strains. Moreso, it was evident that encapsulation of the vaccine with chitosan-saponin nanoparticle further enhanced immune responses and abrogates the need for multiple booster administration of vaccine. Therefore, the bivalent DNA vaccine could serve as efficient and effective alternative strategy for the control of IB in poultry.


Subject(s)
Chitosan/immunology , Coronavirus Infections/veterinary , Infectious bronchitis virus/immunology , Poultry Diseases/immunology , Saponins/immunology , Vaccines, DNA/immunology , Viral Vaccines/immunology , Animals , Antibodies, Viral/immunology , Bronchitis/immunology , Bronchitis/prevention & control , Bronchitis/veterinary , CD8-Positive T-Lymphocytes/immunology , Chickens , Chitosan/chemistry , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Cross Protection , Immunity, Cellular , Immunization, Secondary/veterinary , Immunogenicity, Vaccine , Nanoparticles/chemistry , Poultry Diseases/prevention & control , Saponins/chemistry , Vaccination/veterinary , Vaccines, DNA/chemistry , Vaccines, DNA/genetics , Viral Vaccines/chemistry , Viral Vaccines/genetics
15.
Sci Rep ; 10(1): 16219, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-811544

ABSTRACT

COVID-19 pandemic has resulted in 16,114,449 cases with 646,641 deaths from the 217 countries, or territories as on July 27th 2020. Due to multifaceted issues and challenges in the implementation of the safety and preventive measures, inconsistent coordination between societies-governments and most importantly lack of specific vaccine to SARS-CoV-2, the spread of the virus that initially emerged at Wuhan is still uprising after taking a heavy toll on human life. In the present study, we mapped immunogenic epitopes present on the four structural proteins of SARS-CoV-2 and we designed a multi-epitope peptide based vaccine that, demonstrated a high immunogenic response with a vast application on world's human population. On codon optimization and in-silico cloning, we found that candidate vaccine showed high expression in E. coli and immune simulation resulted in inducing a high level of both B-cell and T-cell mediated immunity. The results predicted that exposure of vaccine by administrating three injections significantly subsidized the antigen growth in the system. The proposed candidate vaccine found promising by yielding desired results and hence, should be validated by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.


Subject(s)
Epitopes/immunology , Molecular Docking Simulation , Vaccines, Subunit/immunology , Viral Vaccines/immunology , Antigen-Antibody Complex/chemistry , Antigen-Antibody Complex/immunology , Antigens, Viral/immunology , B-Lymphocytes/immunology , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Nucleocapsid Proteins , Epitopes/chemistry , HLA Antigens/chemistry , HLA Antigens/immunology , Humans , Immunogenicity, Vaccine , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/immunology , Phosphoproteins , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Toll-Like Receptors/immunology , Vaccines, Subunit/chemistry , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/immunology , Viral Vaccines/chemistry
16.
Infect Dis Poverty ; 9(1): 132, 2020 Sep 16.
Article in English | MEDLINE | ID: covidwho-768657

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. METHODS: Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. RESULTS: Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. CONCLUSION: The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/genetics , Humans , Immunogenicity, Vaccine/immunology , Molecular Docking Simulation , Pneumonia, Viral/immunology , SARS-CoV-2 , Sequence Analysis, Protein , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Toll-Like Receptor 3/chemistry , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/immunology , Vaccines, Subunit/chemistry , Vaccines, Subunit/genetics , Vaccines, Subunit/immunology , Vaccinology/methods , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics
17.
Int J Biol Macromol ; 162: 820-837, 2020 Nov 01.
Article in English | MEDLINE | ID: covidwho-618504

ABSTRACT

SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , RNA, Messenger/immunology , Viral Vaccines/immunology , Betacoronavirus/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Design , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Sequence Analysis, Protein , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics
18.
Indian J Pediatr ; 87(10): 810-816, 2020 10.
Article in English | MEDLINE | ID: covidwho-743773

ABSTRACT

The pandemic declaration of Covid-19 disease by World Health Organization (WHO) and subsequent widespread morbidities and mortalities in almost all countries of the world led to the research and development to find out a vaccine against SARS-CoV2 virus. Normally any new vaccine development takes 10-15 y time but the search for vaccine against SARS-CoV2 is going on at a very fast pace resulting in almost breakthrough in vaccine development by several research institutions and vaccine manufacturers. In pandemic situation, however, the entire process of vaccine development including clinical trials gets shortened and may be fast tracked to 15-18 mo time. It is expected that there shall be simultaneous marketing of several vaccines by the beginning of 2021. There are more than 164 candidate vaccines which are in the process of development and among them 24 vaccines are in advanced stages of development. This review aims at highlighting the present stages of development of vaccines and discussing the challenges that may be faced with these novel vaccines.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Biomedical Research , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Development , Humans , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Vaccines , Viral Vaccines/chemistry , World Health Organization
19.
Infect Genet Evol ; 85: 104517, 2020 11.
Article in English | MEDLINE | ID: covidwho-737519

ABSTRACT

The present study aimed to predict a novel chimeric vaccine by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and normal mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data.


Subject(s)
Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/genetics , SARS-CoV-2/classification , Vaccines, Subunit/genetics , Viral Structural Proteins/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Escherichia coli/genetics , Escherichia coli/growth & development , Evolution, Molecular , Genome, Viral , Humans , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Phylogeny , Protein Conformation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccines, Subunit/chemistry , Vaccines, Subunit/metabolism , Viral Structural Proteins/chemistry , Viral Structural Proteins/immunology , Viral Vaccines/chemistry , Viral Vaccines/genetics , Viral Vaccines/metabolism
20.
Adv Mater ; 32(40): e2004210, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-734755

ABSTRACT

For rapid response against the prevailing COVID-19 (coronavirus disease 19), it is a global imperative to exploit the immunogenicity of existing formulations for safe and efficient vaccines. As the most accessible adjuvant, aluminum hydroxide (alum) is still the sole employed adjuvant in most countries. However, alum tends to attach on the membrane rather than entering the dendritic cells (DCs), leading to the absence of intracellular transfer and process of the antigens, and thus limits T-cell-mediated immunity. To address this, alum is packed on the squalene/water interphase is packed, forming an alum-stabilized Pickering emulsion (PAPE). "Inheriting" from alum and squalene, PAPE demonstrates a good biosafety profile. Intriguingly, with the dense array of alum on the oil/water interphase, PAPE not only adsorbs large quantities of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antigens, but also harbors a higher affinity for DC uptake, which provokes the uptake and cross-presentation of the delivered antigens. Compared with alum-treated groups, more than six times higher antigen-specific antibody titer and three-fold more IFN-γ-secreting T cells are induced, indicating the potent humoral and cellular immune activations. Collectively, the data suggest that PAPE may provide potential insights toward a safe and efficient adjuvant platform for the enhanced COVID-19 vaccinations.


Subject(s)
Adjuvants, Immunologic/chemistry , Viral Vaccines/chemistry , Alum Compounds/chemistry , Animals , Antigens, Viral/chemistry , Antigens, Viral/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Emulsions , HEK293 Cells , Humans , Interferon-gamma/metabolism , Mice, Inbred BALB C , Pandemics , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology
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