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 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 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 A novel Schmallenberg virus subunit vaccine candidate protects IFNAR-/- mice against virulent SBV challenge

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hani Boshra ◽  
Gema Lorenzo ◽  
Diego Charro ◽  
Sandra Moreno ◽  
Gabriel Soares Guerra ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Interferon Γ ◽  
Schmallenberg Virus ◽  
Immune Protection ◽  
Large Ruminant ◽  
Economical Alternative

AbstractSchmallenberg virus (SBV), an arthropod-transmitted pathogenic bunyavirus, continues to be a threat to the European livestock industry, causing morbidity and mortality among young ruminant livestock. Here, we describe a novel SBV subunit vaccine, based on bacterially expressed SBV nucleoprotein (SBV-N) administered with a veterinary-grade Saponin adjuvant. When assayed in an IFNAR-/- mouse model, SBV-N with Saponin induced strong non-neutralizing broadly virus-reactive antibodies, decreased clinical signs, as well as significantly reduced viremia. Vaccination assays also suggest that this level of immune protection is cell mediated, as evidenced by the lack of neutralizing antibodies, as well as interferon-γ secretion observed in vitro. Therefore, based on these results, bacterially expressed SBV-N, co-administered with veterinary-grade Saponin adjuvant may serve as a promising economical alternative to current SBV vaccines, and warrant further evaluation in large ruminant animal models. Moreover, we propose that this strategy may be applicable to other bunyaviruses.

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 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 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.

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 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.

scholarly journals A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice

2020 ◽  
Author(s):  
Claudio Counoupas ◽  
Alberto O. Stella ◽  
Nayan D. Bhattacharyya ◽  
Alice Grey ◽  
Karishma Patel ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Rapid Development ◽  
Population Level ◽  
High Titre ◽  
Spike Protein ◽  
Cold Chain ◽  
Igg Antibody

AbstractNext-generation vaccines that are safe, effective and with equitable access globally are required to prevent SARS-CoV-2 transmission at a population level. One strategy that has gained significant interest is to ‘repurpose’ existing licensed vaccines for use against COVID-19. In this report, we have exploited the immunostimulatory properties of bacille Calmette-Guérin (BCG), the vaccine for tuberculosis, to develop a SARS-CoV-2-specific and highly immunogenic vaccine candidate. Combination of BCG with a stabilized, trimeric form of the SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the sera of vaccinated mice, which could be further augmented by the addition of alum. This vaccine formulation, termed BCG:CoVac, induced a Th1-biased response both in terms of IgG antibody subclass and cytokine release by vaccine-specific CD4+ and CD8+ T cells. A single dose of BCG:CoVac was sufficient to induce high-titre SARS-CoV-2 neutralizing antibodies (NAbs) that were detectable as early as 2 weeks post-vaccination; NAb levels were greater than that seen in the sera of SARS-CoV-2-infected individuals. Boosting of BCG:CoVac-primed mice with a heterologous vaccine combination (spike protein plus alum) could further increase SARS-CoV-2 spike protein-specific antibody response. BCG:CoVac would be broadly applicable for all populations susceptible to SARS-CoV-2 infection and in particular could be readily incorporated into current vaccine schedules in countries where BCG is currently used.ImportanceEffective distribution of vaccine to low- and middle-income countries is critical for the control of the COVID-19 pandemic. To achieve this, vaccines must offer effective protective immunity yet should be cheap to manufacture and meet cold chain management requirements. This study describes a unique COVID-19 vaccine candidate, termed BCG:CoVac, that when delivered as a single dose induces potent SARS-CoV-2 specific immunity in mice, particularly through generation of high-titre, anti-viral neutralising antibodies. BCG:CoVac is built on safe and well-characterised vaccine components: 1) the BCG vaccine, used for control of tuberculosis since 1921 which also has remarkable ‘off target’ effects, protecting children and the elderly against diverse respiratory viral infections; 2) Alhydrogel adjuvant (Alum), a low cost, globally accessible vaccine adjuvant with an excellent safety record in humans (part of >20 licensed human vaccines and in use >70 years); 3) Stabilized, trimeric SARS-CoV-2 spike protein, which stimulates immune specificity for COVID-19. Further assessment in humans will determine if BCG:CoVac can impart protective immunity against not only SARS-CoV-2, but also other respiratory infections where BCG has known efficacy.

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