scholarly journals CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

2021 ◽  
Author(s):  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Tsun-Yung Kuo ◽  
John D Campbell ◽  
Paula Traquina ◽  
...  
Keyword(s):  
Public Health ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Clinical Development ◽  
Spike Protein ◽  
Lung Pathology ◽  
Global Public Health ◽  
Control Groups ◽  
Virus Challenge ◽  
Igg Level

The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 μg or 5 μg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

scholarly journals CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Charles Chen ◽  
Wei-Cheng Lian ◽  
Tsun-Yung Kuo ◽  
...  
Keyword(s):  
Public Health ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Clinical Development ◽  
Spike Protein ◽  
Lung Pathology ◽  
Global Public Health ◽  
Control Groups ◽  
Virus Challenge ◽  
Igg Level

AbstractThe COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

scholarly journals A single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge

2020 ◽  
Author(s):  
Yfat Yahalom-Ronen ◽  
Hadas Tamir ◽  
Sharon Melamed ◽  
Boaz Politi ◽  
Ohad Shifman ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Body Weight Loss ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Lung Pathology ◽  
Golden Syrian Hamster

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 that emerged in December 2019 in China resulted in over 7.8 million infections and over 430,000 deaths worldwide, imposing an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we generated a replication competent recombinant VSV-ΔG-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2. In vitro characterization of the recombinant VSV-ΔG-spike indicated expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in vivo model for COVID-19 was implemented. We show that vaccination of hamsters with recombinant VSV-ΔG-spike results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2. Importantly, single-dose vaccination was able to protect hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss of the immunized hamsters compared to unvaccinated hamsters. Furthermore, whereas lungs of infected hamsters displayed extensive tissue damage and high viral titers, immunized hamsters’ lungs showed only minor lung pathology, and no viral load. Taken together, we suggest recombinant VSV-ΔG-spike as a safe, efficacious and protective vaccine against SARS-CoV-2 infection.

Global Development, Global Public Health, and Ethics

2019 ◽  
pp. 819-829
Author(s):  
Gerald Bloom ◽  
Hayley MacGregor
Keyword(s):  
Public Health ◽  
Health Risks ◽  
Rapid Development ◽  
Rapid Change ◽  
Scientific Discipline ◽  
Global Public Health ◽  
Global Development ◽  
Government Responsibility ◽  
Rapid Urbanization ◽  
Present Context

Rapid development has brought significant economic and health benefits, but it has also exposed populations to new health risks. Public health as a scientific discipline and major government responsibility developed during the nineteenth century to help mitigate these risks. Public health actions need to take into account large inequalities in the benefits and harms associated with development between countries, between social groups, and between generations. This is especially important in the present context of very rapid change. It is important to acknowledge the global nature of the challenges people face and the need to involve countries with different cultures and historical legacies in arriving at consensus on an ethical basis for global cooperation in addressing these challenges. This chapter provides an analysis of these issues, using examples on the management of health risks associated with global development and rapid urbanization and on the emergence of organisms that are resistant to antibiotics.

scholarly journals Impact of HIV-1 Diversity on Its Sensitivity to Neutralization

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 74 ◽  
Author(s):  
Karl Stefic ◽  
Mélanie Bouvin-Pley ◽  
Martine Braibant ◽  
Francis Barin
Keyword(s):  
Public Health ◽  
Envelope Protein ◽  
Neutralizing Antibodies ◽  
Continuous Process ◽  
Population Level ◽  
Global Public Health ◽  
Broadly Neutralizing Antibodies ◽  
The Many ◽  
The Impact ◽  
Hiv 1

The HIV-1 pandemic remains a major burden on global public health and a vaccine to prevent HIV-1 infection is highly desirable but has not yet been developed. Among the many roadblocks to achieve this goal, the high antigenic diversity of the HIV-1 envelope protein (Env) is one of the most important and challenging to overcome. The recent development of broadly neutralizing antibodies has considerably improved our knowledge on Env structure and its interplay with neutralizing antibodies. This review aims at highlighting how the genetic diversity of HIV-1 thwarts current, and possibly future, vaccine developments. We will focus on the impact of HIV-1 Env diversification on the sensitivity to neutralizing antibodies and the repercussions of this continuous process at a population level.

scholarly journals Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020

2020 ◽  
Vol 25 (16) ◽  
Author(s):  
Ranawaka APM Perera ◽  
Chris KP Mok ◽  
Owen TY Tsang ◽  
Huibin Lv ◽  
Ronald LW Ko ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Large Scale ◽  
Herd Immunity ◽  
Cross Reactivity ◽  
Spike Protein ◽  
Infectious Dose ◽  
Virus Challenge ◽  
Illness Onset ◽  
Public Health Decision

Background The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making. Aim Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies. Methods We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT90) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls. Results IgG and IgM RBD ELISA, MN and PRNT90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test. Conclusion Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT90, is a valid approach for large-scale sero-epidemiology studies.

scholarly journals An Adenovirus-Based Vaccine with a Double-Stranded RNA Adjuvant Protects Mice and Ferrets against H5N1 Avian Influenza in Oral Delivery Models

2012 ◽  
Vol 20 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Ciaran D. Scallan ◽  
Debora W. Tingley ◽  
Jonathan D. Lindbloom ◽  
James S. Toomey ◽  
Sean N. Tucker
Keyword(s):  
Avian Influenza ◽  
Oral Delivery ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Adenovirus Vector ◽  
Oral Route ◽  
Lethal Challenge ◽  
Double Stranded Rna ◽  
Virus Challenge ◽  
H5n1 Avian Influenza

ABSTRACTAn oral gene-based avian influenza vaccine would allow rapid development and simplified distribution, but efficacy has previously been difficult to achieve by the oral route. This study assessed protection against avian influenza virus challenge using a chimeric adenovirus vector expressing hemagglutinin and a double-stranded RNA adjuvant. Immunized ferrets and mice were protected upon lethal challenge. Further, ferrets immunized by the peroral route induced cross-clade neutralizing antibodies, and the antibodies were selective against hemagglutinin, not the vector. Similarly, experiments in mice demonstrated selective immune responses against HA with peroral delivery and the ability to circumvent preexisting vector immunity.

scholarly journals Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins

2020 ◽  
Author(s):  
Yuejun Shi ◽  
Jiale Shi ◽  
Limeng Sun ◽  
Yubei Tan ◽  
Gang Wang ◽  
...  
Keyword(s):  
Public Health ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Immune Recognition ◽  
Global Public Health ◽  
S Protein ◽  
Specific Antibodies ◽  
Major Target

AbstractCoronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the “standing” state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the “lying” state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines.ImportanceOutbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein.

scholarly journals Experimental Identification of Immuno- dominant B-cell Epitopes from SARS-CoV-2

2021 ◽  
Vol 75 (4) ◽  
pp. 276-284
Author(s):  
Lluc Farrera-Soler ◽  
Jean-Pierre Daguer ◽  
Sofia Barluenga ◽  
Nicolas Winssinger
Keyword(s):  
Public Health ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Social Impact ◽  
Adaptive Immune Response ◽  
Diagnostic Tools ◽  
Global Public Health ◽  
Health Crisis ◽  
Experimental Identification ◽  
Linear Epitopes

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current public health crisis with devastating consequences to our societies. This COVID-19 pandemic has become the most serious threat to global public health in recent history. Given the unprecedented economic and social impact that it is causing, identification of immunodominant epitopes from SARS-CoV-2 is of great interest, not only to gain better insight into the adaptive immune response, but also for the development of vaccines, treatments and diagnostic tools. In this review, we summarize the already published or preprinted reports on the experimental identification of B-cell linear epitopes of SARS-CoV-2 proteins. Six different epitopes leading to neutralizing antibodies have been identified. Moreover, a summary of peptide candidates to be used for diagnostic tools is also included.

scholarly journals An Intranasal OMV-based vaccine induces high mucosal and systemic protecting immunity against a SARS-CoV-2 infection

2021 ◽  
Author(s):  
Peter A. van der Ley ◽  
Afshin Zariri ◽  
Elly van Riet ◽  
Dinja Oosterhoff ◽  
Corine P. Kruiswijk
Keyword(s):  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Viral Vector ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Peptide Sequence ◽  
Spike Protein ◽  
Control Groups ◽  
Inactivated Vaccines

The development of more effective, accessible and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector and whole inactivated vaccines, is essential to curtain the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six proline stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to Outer Membrane Vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs seven days after challenge in OMV-mC-Spike vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing. 

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.

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