scholarly journals SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

scholarly journals Covid-19 vaccine trials and ethics: Protection delayed is protection denied

2020 ◽  
pp. 01-03
Author(s):  
T Jacob John ◽  
Dhanya Dharmapalan
Keyword(s):  
Large Scale ◽  
Protective Efficacy ◽  
Informed Choice ◽  
Effective Vaccine ◽  
Compassionate Use ◽  
Vaccine Research ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Risk Of Death ◽  
Vaccine Trials

Abstract The Covid-19 pandemic is raging, taking a heavy toll of lives and livelihoods. The need for safe and effective vaccine(s) is urgent. Vaccine research has progressed rapidly and a few vaccine candidates have passed trial Phases 1 and 2, confirming reasonable safety and immunogenicity parameters. They are ready for large scale Phase 3 trials to quantify protective efficacy, if any, and to detect uncommon but serious adverse effects, if any. These developments present unprecedented opportunities and challenges, scientific and ethical. Globally hundreds die every day due to Covid-19, and emergency/compassionate use of vaccine candidates that are ready for Phase 3 trials are likely to save lives. We perceive an ethical imperative to allow such vaccination for those at high risk of death who voluntarily make such an informed choice – for them protection delayed will be tantamount to protection denied.

scholarly journals Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Atin Khalaj-Hedayati
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Subunit Vaccine ◽  
Vaccine Development ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Universal Vaccine ◽  
Health Security ◽  
Vaccine Candidates ◽  
Novel Coronavirus

The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.

scholarly journals Stabilization of the SARS-CoV-2 Spike receptor-binding domain using deep mutational scanning and structure-based design

2021 ◽  
Author(s):  
Daniel Ellis ◽  
Natalie Brunette ◽  
Katherine H. D. Crawford ◽  
Alexandra C. Walls ◽  
Minh N. Pham ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Large Scale ◽  
Protein S ◽  
Binding Pocket ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Generation Vaccine

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.

scholarly journals Stabilization of the SARS-CoV-2 Spike Receptor-Binding Domain Using Deep Mutational Scanning and Structure-Based Design

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Ellis ◽  
Natalie Brunette ◽  
Katharine H. D. Crawford ◽  
Alexandra C. Walls ◽  
Minh N. Pham ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Large Scale ◽  
Protein S ◽  
Binding Pocket ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Generation Vaccine

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.

scholarly journals mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents

2020 ◽  
Author(s):  
Susanne Rauch ◽  
Nicole Roth ◽  
Kim Schwendt ◽  
Mariola Fotin-Mleczek ◽  
Stefan O. Mueller ◽  
...  
Keyword(s):  
Viral Replication ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Protein S ◽  
Scale Production ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Humoral Responses

AbstractThe devastating SARS-CoV-2 pandemic demands rapid vaccine development and large scale production to meet worldwide needs. mRNA vaccines have emerged as one of the most promising technologies to address this unprecedented challenge. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle (LNP) encapsulated non-modified mRNA vaccine that encodes the full length, pre-fusion stabilised SARS-CoV-2 Spike (S) protein. S translated from CVnCoV is cleaved, post-translationally modified, and presented on the cell surface, highlighting the ability of mRNA vaccines to mimic antigen presentation during viral infection. Immunisation with CVnCoV induced strong humoral responses with high titres of virus neutralizing antibodies in mice and hamsters and robust CD4+ and CD8+ T cell responses in mice. Most importantly, vaccination with CVnCoV fully protected hamster lungs from challenge with wild type SARS-CoV-2. To gain insights in the risk of vaccine-enhanced disease, hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication were analysed for signs of vaccine-enhanced disease. No evidence of increased viral replication or exacerbated inflammation and damage to viral target organs was detectable, giving strong evidence for a favourable safety profile of CVnCoV. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

scholarly journals Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 140
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Saied Al-Dehlawi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Protein Production ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
The Novel ◽  
Research Teams ◽  
Advantages And Disadvantages ◽  
Rapid Spread ◽  
New Generation ◽  
Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

scholarly journals Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing

2015 ◽  
Vol 89 (7) ◽  
pp. 3444-3454 ◽  
Author(s):  
Charles N. Agoti ◽  
James R. Otieno ◽  
Patrick K. Munywoki ◽  
Alexander G. Mwihuri ◽  
Patricia A. Cane ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Large Scale ◽  
Vaccine Development ◽  
Human Respiratory Syncytial Virus ◽  
Genomic Variation ◽  
Genomic Sequences ◽  
The Novel ◽  
Sequencing Method ◽  
The World ◽  
Syncytial Virus

ABSTRACTHuman respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.IMPORTANCEThe new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.

From Bench Side to Bed-Travelling on a Road to Get a Safe and Effective Vaccine Against COVID-19, Day to Save the Life

2021 ◽  
Vol 15 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Neutralizing Antibodies ◽  
Cytotoxic T Cells ◽  
Immunological Response ◽  
Surface Protein ◽  
Viral Proteins ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
High Fatality Rate ◽  
Basic Goal ◽  
Epitope Discovery

: Coronavirus Disease 2019 (COVID-19) is caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is the most challenging pandemic of this century. The growing COVID-19 pandemic has triggered extraordinary efforts to restrict the virus in numerous ways, owing to the emergence of SARS-CoV-2. Immunotherapy, which includes artificially stimulating the immune system to generate an immunological response, is regarded as an effective strategy for preventing and treating several infectious illnesses and malignancies. Given the pandemic's high fatality rate and quick expansion, an effective vaccination is urgently needed to keep it under control. The basic goal of all COVID-19 vaccine programs is to develop a vaccine that causes the generation of surface protein neutralizing antibodies in subjects. The epitope discovery for the SARS-CoV-2 vaccine candidates is likewise made using an immuno-informatics methodology. It can be used to find the epitopes in viral proteins important for cytotoxic T cells and B cells. A safe and effective COVID-19 vaccine that can elicit the necessary immune response is necessary to end the epidemic. The global search for a safe and effective COVID-19 vaccine is yielding results. More than a dozen vaccines have already been approved around the world, with many more in the clinical trials. Patents can cover the underlying technology used to generate a vaccine, whereas trade secrets can cover manufacturing methods and procedures.

scholarly journals Vaccines against COVID-19 – Catching the Rays of Hope

2021 ◽  
pp. 469-488
Author(s):  
Suresh Kumar Srinivasamurthy ◽  
Laxminarayana Kurady Bairy
Keyword(s):  
Herd Immunity ◽  
Clinical Impact ◽  
Morbidity And Mortality ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Practical Possibility ◽  
Efficacy Trials ◽  
The World ◽  
The Status ◽  
Early Phase Clinical Trials

COVID-19 pandemic has affected the world in all its dimensions. With herd immunity being a distant and non-practical possibility, vaccination remains most tractable approach to reduce morbidity and mortality. Several early phase clinical trials have proved the immunogenicity of vaccines. The efficacy trials have shown reduction in chance of acquiring COVID-19 disease after vaccination. The vaccines approved for emergency use have reported efficacy above 50% thus making them important public health tool in controlling the pandemic. Nevertheless, several questions remain elusive such as whether these approved vaccines are effective against newer variants of the virus; whether vaccination prevents transmission of the virus in the community; clinical impact of vaccination on morbidity and mortality. This review aims to elucidate the status of vaccine candidates in advanced trials along with the vaccines, which have been granted emergency approvals. Further, we collate the data on vaccines efficacy phase 3 trials and their probability of efficacy against newer variants.

scholarly journals Evidence of antigenic imprinting in sequential Sarbecovirus immunization

2020 ◽  
Author(s):  
Huibin Lv ◽  
Ray T. Y. So ◽  
Meng Yuan ◽  
Hejun Liu ◽  
Chang-Chun D. Lee ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccination Strategy ◽  
Vaccine Effectiveness ◽  
Major Focus ◽  
The World ◽  
The One ◽  
The Impact

SUMMARYAntigenic imprinting, which describes the bias of antibody response due to previous immune history, can influence vaccine effectiveness and has been reported in different viruses. Give that COVID-19 vaccine development is currently a major focus of the world, there is a lack of understanding of how background immunity influence antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting in Sarbecovirus, which is the subgenus that SARS-CoV-2 belongs to. Specifically, we sequentially immunized mice with two antigenically distinct Sarbecovirus strains, namely SARS-CoV and SARS-CoV-2. We found that the neutralizing antibodies triggered by the sequentially immunization are dominantly against the one that is used for priming. Given that the impact of the background immunity on COVID-19 is still unclear, our results will provide important insights into the pathogenesis of this disease as well as COVID-19 vaccination strategy.

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