scholarly journals Polymerized Porin as a Novel Delivery Platform for Coronavirus Vaccine

2021 ◽  
Author(s):  
Zhongqian Yang ◽  
Liangqun Hua ◽  
Mengli Yang ◽  
Weiran Li ◽  
Zhaoling Ren ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Human Life ◽  
Disease Diagnosis ◽  
Immune Memory ◽  
Tumor Vaccines ◽  
Vaccine Platform ◽  
Innovative Drug ◽  
Antigen Uptake ◽  
Delivery Platform ◽  
Cellular Immune

Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. Here, we designed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We use surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane in this study. More importantly, the polymerized RBD displayed on ClyA-RBD polymerized porin (RBD-PP) already has some correct spatial structures of virus spikes. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies and systemic cellular immune responses and immune memory. We applied ofthis PP-based vaccine platform to make an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to be applied to more fields, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis.

scholarly journals Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

2021 ◽  
Author(s):  
Chiara Agrati ◽  
Stefania Capone ◽  
Concetta Castilletti ◽  
Eleonora Cimini ◽  
Giulia Matusali ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Neutralizing Antibodies ◽  
Small Sample Size ◽  
Phase 1 ◽  
Vaccination Campaign ◽  
Small Sample ◽  
Vaccine Platform ◽  
Ideal Tool ◽  
Cellular Immune

Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single administration GRAd-COV2 vaccine candidate in the context of the phase 1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single-dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

scholarly journals Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H. Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies

2021 ◽  
Author(s):  
H. Christian Hong ◽  
Kwang Sung Kim ◽  
Shin Ae Park ◽  
Min Jeong Chun ◽  
Eun Young Hong ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Vero Cells ◽  
Vaccine Platform ◽  
New Era ◽  
European Variant ◽  
Cellular Immune ◽  
And Storage

AbstractIn addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.

scholarly journals Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chiara Agrati ◽  
Stefania Capone ◽  
Concetta Castilletti ◽  
Eleonora Cimini ◽  
Giulia Matusali ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Neutralizing Antibodies ◽  
Small Sample Size ◽  
Phase 1 ◽  
Vaccination Campaign ◽  
Small Sample ◽  
Vaccine Platform ◽  
Ideal Tool ◽  
Cellular Immune

AbstractHere we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single-administration GRAd-COV2 vaccine candidate in the context of the phase-1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T-cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

scholarly journals Evaluation of Clinical and Immune Responses in Recovered Children with Mild COVID-19

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 85
Author(s):  
Xiaodong Tian ◽  
Zhihua Bai ◽  
Ying Cao ◽  
Haizhou Liu ◽  
Di Liu ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Immune Memory ◽  
Lung Lesions ◽  
Significant Difference ◽  
Specific Igg ◽  
Cellular Immune ◽  
Infants And Young Children

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6–8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0–4 years old) had lung lesions that persisted for 6–8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6–8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

scholarly journals A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

2005 ◽  
Vol 86 (5) ◽  
pp. 1435-1440 ◽  
Author(s):  
Milosz Faber ◽  
Elaine W. Lamirande ◽  
Anjeanette Roberts ◽  
Amy B. Rice ◽  
Hilary Koprowski ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Protein S ◽  
S Protein ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune ◽  
Animal Reservoirs ◽  
S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

scholarly journals Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Carolyn Rydyznski ◽  
Keith A. Daniels ◽  
Erik P. Karmele ◽  
Taylor R. Brooks ◽  
Sarah E. Mahl ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
B Cell ◽  
Natural Killer ◽  
Immune Memory ◽  
Killer Cells ◽  
Cell Immunity ◽  
Cellular Immune ◽  
B Cell Immunity

scholarly journals The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients

2018 ◽  
Vol 5 (4) ◽  
pp. 87 ◽  
Author(s):  
Chris Weir ◽  
Annika Oksa ◽  
Jennifer Millar ◽  
Miles Alexander ◽  
Nicola Kynoch ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Tumor Antigens ◽  
Autologous Tumor ◽  
Tumor Vaccines ◽  
Vaccine Platform ◽  
Safety Study ◽  
Diverse Range ◽  
Canine Cancer ◽  
Ongoing Development ◽  
Vaccine Approach

Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.

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