scholarly journals Sterilizing Immunity against SARS‐CoV‐2 Infection in Mice by a Single‐Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist‐Adjuvanted Recombinant Spike Protein Vaccine

2021 ◽  
Author(s):  
Sonia Jangra ◽  
Jana De Vrieze ◽  
Angela Choi ◽  
Raveen Rathnasinghe ◽  
Gabriel Laghlali ◽  
...  
Keyword(s):  
Spike Protein ◽  
Single Shot ◽  
Protein Vaccine ◽  
Sterilizing Immunity

Berichtigung: Sterilizing Immunity against SARS‐CoV‐2 Infection in Mice by a Single‐Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist‐Adjuvanted Recombinant Spike Protein Vaccine

2021 ◽  
Vol 133 (31) ◽  
pp. 16878-16879
Author(s):  
Sonia Jangra ◽  
Jana De Vrieze ◽  
Angela Choi ◽  
Raveen Rathnasinghe ◽  
Gabriel Laghlali ◽  
...  
Keyword(s):  
Spike Protein ◽  
Single Shot ◽  
Protein Vaccine ◽  
Sterilizing Immunity

scholarly journals Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Modified Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine

2020 ◽  
Author(s):  
Sonia Jangra ◽  
Jana De Vrieze ◽  
Angela Choi ◽  
Raveen Rathnasinghe ◽  
Gabriel Laghlali ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Recombinant Protein ◽  
Influenza Viruses ◽  
Water Soluble ◽  
Spike Protein ◽  
Single Shot ◽  
Protein Vaccine ◽  
Adjuvanted Vaccine ◽  
Vaccine Responses

AbstractThe search for vaccines that protect from severe morbidity and mortality as a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is a race against the clock and the virus. Several vaccine candidates are currently being tested in the clinic. Inactivated virus and recombinant protein vaccines can be safe options but may require adjuvants to induce robust immune responses efficiently. In this work we describe the use of a novel amphiphilic imidazoquinoline (IMDQ-PEG-CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol-poly(ethylene glycol) macromolecular amphiphile). This amphiphile is water soluble and exhibits massive translocation to lymph nodes upon local administration, likely through binding to albumin. IMDQ-PEG-CHOL is used to induce a protective immune response against SARS-CoV-2 after single vaccination with trimeric recombinant SARS-CoV-2 spike protein in the BALB/c mouse model. Inclusion of amphiphilic IMDQ-PEG-CHOL in the SARS-CoV-2 spike vaccine formulation resulted in enhanced immune cell recruitment and activation in the draining lymph node. IMDQ-PEG-CHOL has a better safety profile compared to native soluble IMDQ as the former induces a more localized immune response upon local injection, preventing systemic inflammation. Moreover, IMDQ-PEG-CHOL adjuvanted vaccine induced enhanced ELISA and in vitro microneutralization titers, and a more balanced IgG2a/IgG1 response. To correlate vaccine responses with control of virus replication in vivo, vaccinated mice were challenged with SARS-CoV-2 virus after being sensitized by intranasal adenovirus-mediated expression of the human angiotensin converting enzyme 2 (ACE2) gene. Animals vaccinated with trimeric recombinant spike protein vaccine without adjuvant had lung virus titers comparable to non-vaccinated control mice, whereas animals vaccinated with IMDQ-PEG-CHOL-adjuvanted vaccine controlled viral replication and infectious viruses could not be recovered from their lungs at day 4 post infection. In order to test whether IMDQ-PEG-CHOL could also be used to adjuvant vaccines currently licensed for use in humans, proof of concept was also provided by using the same IMDQ-PEG-CHOL to adjuvant human quadrivalent inactivated influenza virus split vaccine, which resulted in enhanced hemagglutination inhibition titers and a more balanced IgG2a/IgG1 antibody response. Enhanced influenza vaccine responses correlated with better virus control when mice were given a lethal influenza virus challenge. Our results underscore the potential use of IMDQ-PEG-CHOL as an adjuvant to achieve protection after single immunization with recombinant protein and inactivated vaccines against respiratory viruses, such as SARS-CoV-2 and influenza viruses.

scholarly journals Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 296
Author(s):  
Jiao Tong ◽  
Chenxi Zhu ◽  
Hanyu Lai ◽  
Chunchao Feng ◽  
Dapeng Zhou
Keyword(s):  
Monoclonal Antibodies ◽  
Vaccine Candidate ◽  
Spike Protein ◽  
Heptad Repeat ◽  
Peptide Array ◽  
Receptor Binding Domain ◽  
Protein Vaccine ◽  
Direct Binding ◽  
Linear Epitopes ◽  
Potent Neutralization

The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 μg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries.

scholarly journals RBD targeted COVID vaccine and full length spike-protein vaccine (mutation and glycosylation role) relationship with procoagulant effect

2021 ◽  
Vol 5 (1) ◽  
pp. 001-008
Author(s):  
M Luisetto ◽  
G Tarro ◽  
Khan Farhan Ahmad ◽  
Edbey Khaled ◽  
GR Mashori ◽  
...  
Keyword(s):  
Regulatory Agency ◽  
Rare Event ◽  
Full Length ◽  
Procoagulant Activity ◽  
Spike Protein ◽  
Relevant Factor ◽  
Vaccine Production ◽  
Protein Vaccine ◽  
Role Relationship ◽  
Procoagulant Effect

Related COVID vaccine production many different strategies was followed by the producers. Observing some rare event of thrombosis after some COVID-19 vaccination, it is interesting to verify if the Target used for the manufacturing can be involved in a different procoagulant activity or not. Some vaccine are suspended in some country or under a deep new verify- investigation by the regulatory agency. (EU or USA). This fact it is relevant. The target SPIKE-PROTEIN FULL LENGTH modified or not or towards the RBD domain can be a relevant factor.

scholarly journals DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss

2021 ◽  
Vol 15 (5) ◽  
pp. e0009374
Author(s):  
Kit Man Chai ◽  
Tsai-Teng Tzeng ◽  
Kuan-Yin Shen ◽  
Hung-Chun Liao ◽  
Jhe-Jhih Lin ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Dna Vaccination ◽  
Spike Protein ◽  
Expression Vectors ◽  
Global Public Health ◽  
Protein Vaccine ◽  
Mammalian Cell Expression ◽  
Cell Expression

The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a nucleic acid-based vaccine is a novel option, beyond the traditional inactivated virus vaccine or recombinant protein vaccine. Here, we report a DNA vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19.

scholarly journals Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pui Wang ◽  
Siu-Ying Lau ◽  
Shaofeng Deng ◽  
Pin Chen ◽  
Bobo Wing-Yee Mok ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
T Cell Response ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Wild Type ◽  
Cleavage Motif ◽  
Sterilizing Immunity

AbstractSARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.

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