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 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 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...

Nanovaccine: A hope to triumph the battle against novel Coronavirus disease 2019 (COVID-19)

2021 ◽  
Vol 15 ◽  
Author(s):  
Anurag Singh ◽  
Anand Maurya ◽  
Gaurav Mishra ◽  
Rajendra Awasthi ◽  
Kamal Dua ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Goblet Cells ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Infection Site ◽  
Peptide Vaccines ◽  
Ciliated Cells ◽  
Novel Coronavirus ◽  
Major Target

Background: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. Methods: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. Results: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/ subunit protein vaccines, peptide vaccines, and virus-like particles etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into clinical trials. Conclusion: : Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

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 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 Piglet immunization with a spike subunit vaccine enhances disease by porcine epidemic diarrhea virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jieshi Yu ◽  
Chithra Sreenivasan ◽  
Tirth Uprety ◽  
Rongyuan Gao ◽  
Chen Huang ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Development ◽  
Spike Protein ◽  
Vaccine Research ◽  
Disease Symptoms ◽  
Diarrhea Virus ◽  
Cell Lysate ◽  
Porcine Epidemic Diarrhea

AbstractImmunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.

scholarly journals Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodiesIdentification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

2021 ◽  
Author(s):  
Lin Li ◽  
Zhongpeng Zhao ◽  
Xiaolan Yang ◽  
Wendong Li ◽  
Shaolong Chen ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
Effective Vaccine ◽  
B Cell Epitopes ◽  
S Protein ◽  
B Cell Epitope ◽  
Linear B

Abstract SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with pooled serum antibodies from horses, mice, and monkeys inoculated with different SARS-CoV-2 vaccine candidates or five patients recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

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 SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Comparison of Four SARS-CoV-2 Neutralization Assays

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Lydia Riepler ◽  
Annika Rössler ◽  
Albert Falch ◽  
André Volland ◽  
Wegene Borena ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
The Other ◽  
In Vitro Assays ◽  
The Novel ◽  
Effective Protection ◽  
Vaccine Candidates ◽  
Vesicular Stomatitis ◽  
Novel Coronavirus

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

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