scholarly journals Development of an inactivated vaccine candidate for SARS-CoV-2

Science ◽  
2020 ◽  
Vol 369 (6499) ◽  
pp. 77-81 ◽  
Author(s):  
Qiang Gao ◽  
Linlin Bao ◽  
Haiyan Mao ◽  
Lin Wang ◽  
Kangwei Xu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Rapid Development ◽  
Pilot Scale ◽  
Scale Production ◽  
Complete Protection ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Different Doses

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2–specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2–specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.

scholarly journals Rapid development of an inactivated vaccine for SARS-CoV-2

2020 ◽  
Author(s):  
Qiang Gao ◽  
Linlin Bao ◽  
Haiyan Mao ◽  
Lin Wang ◽  
Kangwei Xu ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Vaccine Candidate ◽  
Rapid Development ◽  
Clinical Signs ◽  
Pilot Scale ◽  
Systematic Evaluation ◽  
Scale Production ◽  
Complete Protection

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans.One Sentence SummaryA purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology

scholarly journals Development of Inactivated FAKHRAVAC® Vaccine against SARS-CoV-2 Virus: Preclinical Study in Animal Models

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1271
Author(s):  
Soheil Ghasemi ◽  
Kosar Naderi Saffar ◽  
Firooz Ebrahimi ◽  
Pezhman Khatami ◽  
Arina Monazah ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Rhesus Macaques ◽  
Seroconversion Rate ◽  
Pilot Scale ◽  
Preclinical Study ◽  
Scale Production ◽  
Global Public Health ◽  
Health Crisis

The recent viral infection disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis. Iran, as one of the countries that reported over five million infected cases by September 2021, has been concerned with the urgent development of effective vaccines against SARS-CoV-2. In this paper, we report the results of a study on potency and safety of an inactivated SARS-CoV-2 vaccine candidate (FAKHRAVAC) in a preclinical study so as to confirm its potential for further clinical evaluation. Here, we developed a pilot-scale production of FAKHRAVAC, a purified inactivated SARS-CoV-2 virus vaccine candidate that induces neutralizing antibodies in Balb/c mice, guinea pigs, rabbits, and non-human primates (Rhesus macaques—RM). After obtaining ethical code of IR.IUMS.REC.1399.566, immunizations of animals were conducted by using either of three different vaccine dilutions; High (H): 10 μg/dose, Medium (M): 5 μg/dose, and Low (L): 1 μg/dose, respectively. In the process of screening for viral seeds, viral strains that resulted in the most severe clinical manifestation in patients have been isolated for vaccine development. The viral seed produced the optimal immunity against SARS-CoV-2 virus, which suggests a possible broader neutralizing ability against SARS-CoV-2 strains. The seroconversion rate at the H-, M-, and L-dose groups of all tested animals reached 100% by 28 days after immunization. These data support the eligibility of FAKHRAVAC vaccine candidate for further evaluation in a clinical trial.

scholarly journals PRAK-03202: A triple antigen VLP vaccine candidate against SARS CoV-2

2020 ◽  
Author(s):  
Saumyabrata Mazumder ◽  
Ruchir Rastogi ◽  
Avinash Undale ◽  
Kajal Arora ◽  
Nupur Mehrotra Arora ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Rapid Development ◽  
Humoral Response ◽  
T Helper 1 ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Neutralizing Potential ◽  
Cellular Immune ◽  
Different Doses

AbstractThe rapid development of safe and effective vaccines against SARS CoV-2 is the need of the hour for the coronavirus outbreak. Here, we have developed PRAK-03202, the world’s first triple antigen VLP vaccine candidate in a highly characterized S. cerevisiae-based D-CryptTM platform, which induced SARS CoV-2 specific neutralizing antibodies in BALB/c mice. Immunizations using three different doses of PRAK-03202 induces antigen specific (Spike, envelope and membrane proteins) humoral response and neutralizing potential. PBMCs from convalescent patients, when exposed to PRAK-03202, showed lymphocyte proliferation and elevated IFN-γ levels suggestive of conservation of epitopes and induction of T helper 1 (Th1)–biased cellular immune responses. These data support the clinical development and testing of PRAK-03202 for use in humans.

scholarly journals Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

2020 ◽  
Author(s):  
Jesse H. Erasmus ◽  
Amit P. Khandhar ◽  
Alexandra C. Walls ◽  
Emily A. Hemann ◽  
Megan A. O’Connor ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Scale Up ◽  
Igg Antibody ◽  
Antibody Isotypes ◽  
Rna Replicon

AbstractThe ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

scholarly journals Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice

2020 ◽  
Author(s):  
Shihui Sun ◽  
Lei He ◽  
Zhongpeng Zhao ◽  
Hongjing Gu ◽  
Xin Fang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Macaca Fascicularis ◽  
Protective Efficacy ◽  
Phase 1 ◽  
Pilot Scale ◽  
Scale Production ◽  
Human Igg1 ◽  
Clinical Trails ◽  
Human Primate

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to infect people globally. The increased COVID-19 cases and no licensed vaccines highlight the need to develop safe and effective vaccines against SARS-CoV-2 infection. Multiple vaccines candidates are under pre-clinical or clinical trails with different strengths and weaknesses. Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and human ACE2 transgenic mice. The antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, suggesting a broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively. These data support clinical development of SARS-CoV-2 vaccines for humans. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails.SummaryThis study confirms protective efficacy of a SARS-CoV-2 RBD-Fc subunit vaccine.

Whole Inactivated Virus and Protein-Based COVID-19 Vaccines

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Peter J. Hotez ◽  
Maria Elena Bottazzi
Keyword(s):  
Neutralizing Antibodies ◽  
Scientific Community ◽  
Nonhuman Primates ◽  
Rapid Development ◽  
Annual Review ◽  
Publication Date ◽  
Middle Income ◽  
Middle Income Countries ◽  
Cell Responses ◽  
Protein Particle

The rapid development and deployment of mRNA and adenovirus-vectored vaccines against coronavirus disease 2019 (COVID-19) continue to astound the global scientific community, but these vaccine platforms and production approaches have still not achieved global COVID-19 vaccine equity. Immunizing the billions of people at risk for COVID-19 in the world's low- and middle-income countries (LMICs) still relies on the availability of vaccines produced and scaled through traditional technology approaches. Vaccines based on whole inactivated virus (WIV) and protein-based platforms, as well as protein particle-based vaccines, are the most produced by LMIC vaccine manufacturing strategies. Three major WIV vaccines are beginning to be distributed widely. Several protein-based and protein particle-based vaccines are advancing with promising results. Overall, these vaccines are exhibiting excellent safety profiles and in some instances have shown their potential to induce high levels of virus neutralizing antibodies and T cell responses (and protection) both in nonhuman primates and in early studies in humans. There is an urgent need to continue accelerating these vaccines for LMICs in time to fully vaccinate these populations by the end of 2022 at the latest. Achieving these goals would also serve as an important reminder that we must continue to maintain expertise in producing multiple vaccine technologies, rather than relying on any individual platform. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joshua G. Liang ◽  
Danmei Su ◽  
Tian-Zhang Song ◽  
Yilan Zeng ◽  
Weijin Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Rna Viruses ◽  
Rhesus Macaques ◽  
Rapid Development ◽  
Host Cells ◽  
Water Emulsion ◽  
Oil In Water Emulsion ◽  
High Level

AbstractSARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

scholarly journals Multi-kernel CNN block-based detection for COVID-19 with imbalance dataset

2021 ◽  
Vol 11 (3) ◽  
pp. 2467
Author(s):  
Muhammad Khaerul Naim Mursalim ◽  
Ade Kurniawan
Keyword(s):  
Deep Learning ◽  
Rapid Development ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Kernel Convolution ◽  
Proposed Model ◽  
Chest X Ray ◽  
Classification Tasks ◽  
Block Based ◽  
Level Performance

COVID-19, which originated from Wuhan, rapidly spread throughout the world and became a public health crisis. Recognizing the positive cases at the earliest stage was crucial in order to restrain the spread of this virus and to perform medical treatment quickly for patients affected. However, the limited supply of RT-PCR as a diagnosis tool caused greatly delay in obtaining examination results of the suspected patients. Previous research stated that using radiologic images could be utilized to detect COVID-19 before the symptoms appeared. With the rapid development of Artificial intelligence in medical imaging in recent years, deep learning as the core of this technology could achieve human-level-performance in diagnostic accuracy. In this paper, deep learning was implemented to detect COVID-19 using a chest X-ray dataset. The proposed model employed a multi-kernel convolution neural network (CNN) block combined with pre-trained ResNet-34 to overcome an imbalanced dataset. The model block adopted different kernel sizes as follows 1x1, 3x3, 5x5, and 7x7. The findings show that the proposed model is capable of performing binary and three class classification tasks with an accuracy of 100% and 93.51% in the validation phase and 95% and 83% in the test phase, respectively.

scholarly journals A Rational Design of a Multi-Epitope Vaccine Against SARS-CoV-2 Which Accounts for the Glycan Shield of the Spike Glycoprotein

2020 ◽  
Author(s):  
William R. Martin ◽  
Feixiong Cheng
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
Rational Design ◽  
Vaccine Candidate ◽  
Rapid Development ◽  
Spike Glycoprotein ◽  
Epitope Vaccine ◽  
Effective Prevention ◽  
Health Crisis ◽  
Vaccine Candidates

<p>The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 (COVID-19) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is yet to be a proven effective treatment or cure for COVID-19. In this study, we have presented a synergistic computational platform, including molecular dynamics simulations and immunoinformatics techniques, to rationally design a multi-epitope vaccine candidate for COVID-19. This platform combines epitopes across Linear B Lymphocytes (LBL), Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocytes (HTL) derived from both mutant and wild-type spike glycoproteins from SARS-CoV-2 with diverse protein conformations. In addition, this vaccine construct also takes the considerable glycan shield of the spike glycoprotein into account, which protects it from immune response. We have identified a vaccine candidate (a 35.9 kDa protein), named COVCCF, which is composed of 5 LBL, 6 HTL, and 6 CTL epitopes from the spike glycoprotein of SARS-CoV-2. Using multi-dose immune simulations, COVCCF induces elevated levels of immunoglobulin activity (IgM, IgG1, IgG2), and induces strong responses from B lymphocytes, CD4 T-helper lymphocytes, and CD8 T-cytotoxic lymphocytes. COVCCF induces cytokines important to innate immunity, including IFN-γ, IL4, and IL10. Additionally, COVCCF has ideal pharmacokinetic properties and low immune-related toxicities. In summary, this study provides a powerful, computational vaccine design platform for rapid development of vaccine candidates (including COVCCF) for effective prevention of COVID-19.</p>

scholarly journals Pilot-Scale Production and Characterization of Paramyosin, a Vaccine Candidate for Schistosomiasis Japonica

2008 ◽  
Vol 76 (7) ◽  
pp. 3164-3169 ◽  
Author(s):  
Mario Jiz ◽  
Hai-Wei Wu ◽  
Rui Meng ◽  
Sunthorn Pond-Tor ◽  
Mindy Reynolds ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Sodium Dodecyl ◽  
Public Health Problem ◽  
Pilot Scale ◽  
Size Exclusion ◽  
Major Public Health Problem ◽  
Scale Production ◽  
Pilot Scale Production

ABSTRACT Despite effective chemotherapy, schistosomiasis remains a major public health problem in the developing world, with at least 200 million active infections resulting in significant morbidity. Rapid reinfection after treatment, accompanied by extensive residual morbidity, mandates alternative control strategies, including vaccine development. Paramyosin, a myofibrillar protein found only in invertebrates, has been widely studied as a vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Recently, we demonstrated that Th2-biased immune responses to paramyosin are associated with resistance to reinfection with S. japonicum in humans; however, challenges in the pilot-scale production of schistosome paramyosin have hampered further studies of this promising vaccine candidate. Here we report a method for the pilot-scale expression and purification of recombinant S. japonicum paramyosin (rSj97). rSj97 was extracted from Escherichia coli inclusion bodies and purified with sequential anion-exchange, hydroxyapatite, and size exclusion chromatography. The purified rSj97 was >95% pure as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis and was free of significant endotoxin contamination. We demonstrate that, like native paramyosin, rSj97 adopts an alpha-helical coiled-coil tertiary structure and binds immunoglobulin and collagen. Naïve mice infected with S. japonicum produce anti-rSj97 immunoglobulin G (IgG) antibodies as early as 4 weeks postinfection, while sera collected from S. japonicum-infected individuals contain anti-rSj97 IgE antibodies. Our method for pilot-scale production of recombinant full-length paramyosin will facilitate preclinical evaluation of paramyosin as a vaccine for schistosomiasis.

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