scholarly journals Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine

2021 ◽  
Author(s):  
Jian Hang Lam ◽  
Amit Kumar Khan ◽  
Thomas Andrew Cornell ◽  
Regine Josefine Dress ◽  
Teck Wan Chia ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Adaptive Immune Response ◽  
Cationic Lipid ◽  
Spike Protein ◽  
Protein Subunit ◽  
Vaccine Platform ◽  
Self Assembling ◽  
Generation Vaccine ◽  
Efficacious Vaccine ◽  
Th1 Cytokines

AbstractMultiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+ and CD8+ T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.

scholarly journals Broad and Long-lasting Immune Response against SARS-CoV-2 Omicron and Other Variants by PIKA-Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine (YS-SC2-010)

2021 ◽  
Author(s):  
Yuan Liu ◽  
Nan Zhang ◽  
Bin Wang ◽  
Yi Zhang
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Subunit Vaccine ◽  
Extended Period ◽  
Immune Serum ◽  
Spike Protein ◽  
Protein Subunit ◽  
Neutralization Activity ◽  
The World ◽  
Mutant Strains

Recently SARS-CoV-2 Omicron (B.1.1.529) variant was identified in South Africa with numerous mutations in spike protein, and numerous community infections have been reported and raised grave concern around the world. Some studies found that the neutralization effects of several licensed vaccines against Omicron were dramatically reduced, which significantly affected antibody mediated protection, especially for individuals whose immunization were completed after extended period. In this regard, we studied the persistence and neutralization activity toward mutant strains in animal serum immunized with PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine (YS-SC2-010). Here we are reporting that animal serum collected at 596 days after immunization with YS-SC2-010 still retains high and persistent neutralizing activity against all the Variant of Concern (VOC) variants, including Omicron variant. Although it is a blessed event to achieve 20 months long neutralization against Omicron variant after immunization with YS-SC2-010, it was also founded that the neutralization effect of immune serum on Omicron decreased by 6.29 folds as compared to D614G, more significantly when compared with other mutant strains.

scholarly journals Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates

2013 ◽  
Vol 26 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Jie Li ◽  
Laura Ulitzky ◽  
Erica Silberstein ◽  
Deborah R. Taylor ◽  
Raphael Viscidi
Keyword(s):  
Subunit Vaccine ◽  
Spike Protein ◽  
Sars Coronavirus ◽  
Protein Subunit ◽  
Vaccine Candidates ◽  
Protection Efficacy

scholarly journals Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine

ACS Nano ◽  
2021 ◽  
Author(s):  
Jian Hang Lam ◽  
Amit K. Khan ◽  
Thomas A. Cornell ◽  
Teck Wan Chia ◽  
Regine J. Dress ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Spike Protein ◽  
Protein Subunit

scholarly journals Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaiʻi Lineage B.1.243

2021 ◽  
Author(s):  
David P Maison ◽  
Lauren L Ching ◽  
Sean B Cleveland ◽  
Alanna C Tseng ◽  
Eileen Nakano ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Predictive Value ◽  
Vaccine Design ◽  
Spike Protein ◽  
Clinical Samples ◽  
Strong Positive Correlation ◽  
Vaccine Platform ◽  
Prevalence Data ◽  
Generation Vaccine ◽  
R Value

SARS-CoV-2 worldwide emergence and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired clinical samples, analyzed SARS-CoV-2 genomes, used the most worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the SARS-CoV-2 vaccine platform. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson's correlation determines exponential emergence. The SARS-CoV-2 genome evaluation indicated 49 mutations. Nine of the ten most worldwide prevalent (>70%) spike protein changes have r-values >0.9. The tenth, D614G, has a prevalence >99% and r-value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. SARS-CoV-2 is predicted to remain endemic and continues to evolve, so must SARS-CoV-2 monitoring and next-generation vaccine design.

scholarly journals SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marta Ferreira-Gomes ◽  
Andrey Kruglov ◽  
Pawel Durek ◽  
Frederik Heinrich ◽  
Caroline Tizian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Reaction ◽  
Adaptive Immune Response ◽  
Gene Expression Signature ◽  
Spike Protein ◽  
Single Cell Level ◽  
Cell Level ◽  
Adaptive Immune

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

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 Replication, pathogenicity, and transmission of SARS-CoV-2 in minks

2020 ◽  
Author(s):  
Lei Shuai ◽  
Gongxun Zhong ◽  
Quan Yuan ◽  
Zhiyuan Wen ◽  
Chong Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Severe Acute Respiratory Syndrome ◽  
Subunit Vaccine ◽  
Lung Damage ◽  
Spike Protein ◽  
Pulmonary Lesions ◽  
Potential Strategy ◽  
Respiratory Droplets

Abstract Minks are raised in many countries and have transmitted severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) to humans. However, the biologic properties of SARS-CoV-2 in minks are largely unknown. Here, we investigated and found that SARS-CoV-2 replicates efficiently in both the upper and lower respiratory tracts, and transmits efficiently in minks via respiratory droplets; pulmonary lesions caused by SARS-CoV-2 in minks are similar to those seen in humans with COVID-19. We further found that a spike protein-based subunit vaccine largely prevented SARS-CoV-2 replication and lung damage caused by SARS-CoV-2 infection in minks. Our study indicates that minks are a useful animal model for evaluating the efficacy of drugs or vaccines against COVID-19 and that vaccination is a potential strategy to prevent minks from transmitting SARS-CoV-2.

scholarly journals Combination of a Sindbis-SARS-CoV-2 spike vaccine and αOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity

2021 ◽  
Author(s):  
Antonella Scaglione ◽  
Silvana Opp ◽  
Alicia Hurtado ◽  
Christine Pampeno ◽  
Ziyan Lin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Immunity ◽  
T Cell Response ◽  
Spike Protein ◽  
Effector Memory ◽  
World Population ◽  
Vaccine Platform ◽  
Vaccine Approach

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the world population at record speeds. However, there is still demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the SARS-CoV-2 spike protein (SV.Spike), combined with the OX40 immunostimulatory antibody (OX40) as a novel, highly effective vaccine approach. We show that SV.Spike plus αOX40 elicits long-lasting neutralizing antibodies and a vigorous T cell response in mice. Protein binding, immunohistochemical and cellular infection assays all show that vaccinated mice sera inhibits spike functions. Immunophenotyping, RNA Seq transcriptome profiles and metabolic analysis indicate a reprogramming of T cells in vaccinated mice. Activated T cells were found to mobilize to lung tissue. Most importantly, SV.Spike plus αOX40 provided robust immune protection against infection with authentic coronavirus in transgenic mice expressing the human ACE2 receptor (hACE2-Tg). Finally, our immunization strategy induced strong effector memory response, potentiating protective immunity against re-exposure to SARS-CoV-2 spike protein. Our results show the potential of a new Sindbis virus-based vaccine platform to counteract waning immune response that can be used as a new candidate to combat SARS-CoV-2. Given the strong T cell responses elicited, our vaccine is likely to be effective against variants that are proving challenging, as well as, serve as a platform to develop a broader spectrum pancoronavirus vaccine. Similarly, the vaccine approach is likely to be applicable to other pathogens.

scholarly journals A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates

2021 ◽  
Author(s):  
Neil C Dalvie ◽  
Lisa H Tostanoski ◽  
Sergio A Rodriguez-Aponte ◽  
Kawaljit Kaur ◽  
Sakshi Bajoria ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Subunit Vaccine ◽  
Hepatitis B Surface Antigen ◽  
Low Cost ◽  
Humoral Response ◽  
High Volume ◽  
Developed Countries ◽  
Protein Subunit ◽  
Middle Income

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

scholarly journals Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

2021 ◽  
Author(s):  
Tsun-Yung Kuo ◽  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Meei-Yun Lin ◽  
Chung-Chin Wu ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Virus Titer ◽  
Neutralizing Antibody ◽  
Protein S ◽  
Protein Subunit ◽  
Live Virus ◽  
The Third ◽  
Severity Of Disease ◽  
Potent Immune Response ◽  
Ancestral Strain

AbstractThe current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines, increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) adjuvanted with CpG 1018 and aluminum hydroxide. Here we used the Delta variant to challenge hamsters innoculated with S-2P based on the ancestral strain or the Beta variant in two-dose or three-dose regimens. Two doses of ancestral S-2P followed by the third dose of Beta variant S-2P was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the ancestral strain as well as all VoCs. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and reduce lung live virus titer. Three doses of vaccination significantly reduced lung viral RNA titer, regardless of using the ancestral or Beta variant S-2P as the third dose. Based on the immunogenicity and viral challenge data, two doses of ancestral S-2P followed by the third dose of Beta variant S-2P could induce broad and potent immune response against the variants.

Sign in / Sign up

Export Citation Format

Share Document