scholarly journals A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains

2020 ◽  
Author(s):  
Bethany Dearlove ◽  
Eric Lewitus ◽  
Hongjun Bai ◽  
Yifan Li ◽  
Daniel B. Reeves ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Sequence Diversity ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Virus Spread ◽  
Vaccine Candidates ◽  
Human Host

AbstractThe magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Here we analyzed SARS-CoV-2 sequence diversity across 5,700 sequences sampled since December 2019. The Spike protein, which is the target immunogen of most vaccine candidates, showed 93 sites with shared polymorphisms; only one of these mutations was found in more than 1% of currently circulating sequences. The minimal diversity found among SARS-CoV-2 sequences can be explained by drift and bottleneck events as the virus spread away from its original epicenter in Wuhan, China. Importantly, there is little evidence that the virus has adapted to its human host since December 2019. Our findings suggest that a single vaccine should be efficacious against current global strains.One Sentence SummaryThe limited diversification of SARS-CoV-2 reflects drift and bottleneck events rather than adaptation to humans as the virus spread.

scholarly journals A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants

2020 ◽  
Vol 117 (38) ◽  
pp. 23652-23662 ◽  
Author(s):  
Bethany Dearlove ◽  
Eric Lewitus ◽  
Hongjun Bai ◽  
Yifan Li ◽  
Daniel B. Reeves ◽  
...  
Keyword(s):  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Spike Protein ◽  
Reference Sequence ◽  
Viral Population ◽  
Effective Vaccine ◽  
Nucleotide Substitutions ◽  
Bioinformatics Analyses ◽  
Vaccine Candidates

The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages.

scholarly journals A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Izabela K Ragan ◽  
Lindsay M Hartson ◽  
Taru S Dutt ◽  
Andres Obregon-Henao ◽  
Rachel M Maison ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Rapid Development ◽  
Neutralizing Antibody ◽  
Emerging Diseases ◽  
Effective Vaccine ◽  
Preliminary Evaluation ◽  
Sequencing Data ◽  
Post Challenge ◽  
Vaccine Candidates ◽  
The Impact

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

scholarly journals Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates

2021 ◽  
Author(s):  
Qingyu Zhao ◽  
Yanan Gao ◽  
Min Xiao ◽  
Xuefei Huang ◽  
Xuanjun Wu
Keyword(s):  
Synthetic Peptide ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Vaccine Candidates ◽  
Peptide Epitopes ◽  
Novel Coronavirus ◽  
Immunological Evaluation

For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have...

scholarly journals Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach

2020 ◽  
Author(s):  
Rohit Pritam Das ◽  
Manaswini Jagadeb ◽  
Surya Narayan Rath
Keyword(s):  
Global Health ◽  
Viral Infection ◽  
B Cell ◽  
Molecular Interaction ◽  
Vaccine Candidate ◽  
Virus Disease ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Mhc Molecules ◽  
Peptide Candidate

Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.

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 BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response

2020 ◽  
Author(s):  
Juwel Chandra Baray ◽  
Md. Maksudur Rahman Khan ◽  
Asif Mahmud ◽  
Md. Jikrul Islam ◽  
Sanat Myti ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Hek293 Cells ◽  
Effective Vaccine ◽  
Great Promise ◽  
Dependent Manner ◽  
Preclinical Trial ◽  
Almost All

AbstractEffective vaccine against SARS-CoV-2 is the utmost importance in the current world. More than 1 million deaths are accounted for relevant pandemic disease COVID-19. Recent data showed that D614G genotype of the virus is highly infectious and responsible for almost all infection for 2nd wave. Despite of multiple vaccine development initiatives, there are currently no report that has addressed this critical variant D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine considering the D614G variant and characterization of the vaccine in preclinical trial. The surface plasmon resonance (SPR) data with spike protein as probe and competitive neutralization with RBD and S2 domain revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, immunization protected mice lungs from pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The IgG2a to IgG1 and (IgG2a+IgG2b) to (IgG1+IgG3) ratios were found 1±0.2 and 1.24±0.1, respectively. These values are comparatively higher than relevant values for other published SARS-CoV-2 vaccine in development,1, 2 and suggesting higher viral clearance capacity for our vaccine. The data suggested great promise for immediate translation of the technology to the clinic.

scholarly journals Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

Science ◽  
2020 ◽  
Vol 370 (6520) ◽  
pp. 1089-1094 ◽  
Author(s):  
Sandhya Bangaru ◽  
Gabriel Ozorowski ◽  
Hannah L. Turner ◽  
Aleksandar Antanasijevic ◽  
Deli Huang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Structural Integrity ◽  
Vaccine Candidate ◽  
Full Length ◽  
Spike Protein ◽  
Primary Target ◽  
Site Specific ◽  
Vaccine Candidates

Vaccine efforts to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo–election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax, which is based on a full-length spike protein formulated in polysorbate 80 detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures. We also observed interactions between the spike trimers, allowing formation of higher-order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

scholarly journals Evolution of SARS-CoV-2 virus and assessment of the effectiveness of COVID-19 vaccine

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 28
Author(s):  
Veljko Veljkovic ◽  
Vladimir Perovic ◽  
Isabelle Chambers ◽  
Slobodan Paessler
Keyword(s):  
Viral Replication ◽  
Reference Strain ◽  
Vaccine Development ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
Proof Reading

A safe and effective vaccine is urgently needed to bring the current SARS-CoV-2 pandemic under control. The spike protein (SP) of SARS-CoV-2 represents the principal target for most vaccines currently under development. Despite the presence of a CoV proof-reading function in viral replication, SP protein from SARS-CoV still extensively mutates, which might have an impact on current and future vaccine development. Here, we present analysis of more than 1600 SP unique variants suggesting that vaccine candidates based on the Wuhan-Hu-1 reference strain would be effective against most of currently circulated SARS-CoV-2 viruses, but that further monitoring of the evolution of this virus is important for identification of other mutations, which could affect the effectiveness of vaccines.

scholarly journals Prediction of the effectiveness of COVID-19 vaccine candidates

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 365 ◽  
Author(s):  
Veljko Veljkovic ◽  
Vladimir Perovic ◽  
Slobodan Paessler
Keyword(s):  
Spike Protein ◽  
Effective Vaccine ◽  
Vaccine Candidates

A safe and effective vaccine is urgently needed to bring the current SARS-CoV-2 pandemic under control. The spike protein (SP) of SARS-CoV-2 represents the principal target for most vaccines currently under development. This protein is highly conserved indicating that vaccine based on this antigen will be efficient against all currently circulating SARS-CoV-2 strains. The present analysis of SP suggests that mutation D614G could significantly decrease the effectiveness of the COVID-19 vaccine through modulation of the interaction between SARS-CoV-2 and its principal receptor ACE2.

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