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Open accessJournal ArticleDOI: 10.1038/S41467-021-21639-W

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques.

02 Mar 2021-Nature Communications (Nature Publishing Group)-Vol. 12, Iss: 1, pp 1386-1386
Abstract: The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

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Topics: Immunogenicity (55%)
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27 results found


Open accessJournal ArticleDOI: 10.1021/ACSCENTSCI.1C00120
Yingzhu Li1, Rumiana Tenchov1, Jeffrey Smoot1, Cynthia Liu1  +2 moreInstitutions (1)
Abstract: This report examines various vaccine platforms including inactivated vaccines, protein-based vaccines, viral vector vaccines, and nucleic acid (DNA or mRNA) vaccines, and their ways of producing immunogens in cells.

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Topics: Viral vector (53%)

51 Citations


Open accessPosted ContentDOI: 10.1101/2021.06.30.21259439
02 Jul 2021-medRxiv
Abstract: BackgroundWe report the clinical efficacy against COVID-19 infection of BBV152, a whole-virion inactivated SARS-CoV-2 vaccine formulated with a Toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG). MethodsWe did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18-98 years) randomised 1:1 using a computer-generated randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory-confirmed symptomatic COVID-19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in sub-groups for age (18-< 60 years and [≥] 60 years) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots. FindingsBetween November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0{middle dot}77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77{middle dot}8% (95% CI: 65{middle dot}2-86{middle dot}4). Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93{middle dot}4% (57{middle dot}1-99{middle dot}8). Efficacy against asymptomatic COVID-19 was 63{middle dot}6% (29{middle dot}0-82{middle dot}4). BBV152 conferred 65{middle dot}2% (95% CI: 33{middle dot}1-83{middle dot}0) protection against the SARS-CoV-2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported. InterpretationBBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID-19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines. FundingThis work was supported and funded by Bharat Biotech International Limited and partly co-funded by the Indian Council of Medical Research. Clinicaltrials.gov: NCT04641481

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Topics: Vaccine efficacy (55%)

24 Citations


Open accessJournal ArticleDOI: 10.3390/PH14050406
Zhipeng Yan1, Ming Yang1, Ching-Lung Lai1Institutions (1)
25 Apr 2021-Pharmaceuticals
Abstract: Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.

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Topics: Herd immunity (51%), Vaccination (51%)

19 Citations


Open accessJournal ArticleDOI: 10.1016/J.ISCI.2021.102298
23 Apr 2021-iScience
Abstract: We report the development and evaluation of safety and immunogenicity of a whole virion inactivated (WVI) SARS-CoV-2 vaccine (BBV152), adjuvanted with aluminum hydroxide gel (Algel), or TLR7/8 agonist chemisorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established Vero cell platform to produce large-scale GMP-grade highly purified inactivated antigen. Product development and manufacturing process were carried out in a BSL-3 facility. Immunogenicity and safety were determined at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers (NAb), at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation contains TLR7/8 agonist adjuvant-induced Th1-biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2-specific IFN-γ+ CD4+ T lymphocyte response. Our results support further development for phase I/II clinical trials in humans.

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Topics: Inactivated vaccine (64%), Immunogenicity (57%), Neutralizing antibody (53%) ... show more

16 Citations


Open accessPosted ContentDOI: 10.1101/2021.04.07.21255078
13 Apr 2021-medRxiv
Abstract: BackgroundTwo vaccines are currently being administered in India to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the humoral immune response after the first dose of two vaccines ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) in Indian health care workers (HCW). MethodsThis ongoing, Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study is being conducted amongst HCW, with or without past history of SARS-CoV-2 infection. SARS-CoV-2 anti-spike binding antibody is being assessed quantitatively at four timepoints between 21 days or more after the first dose to 6 months after the second dose. Primary aim is to analyze antibody response following each dose of both vaccines and its correlation to age, sex, body mass index (BMI) and comorbidities. Here we report the preliminary results of anti-spike antibody response after the first dose. ResultsAmongst the 552 HCW (325 Male, 227 Female), 456 and 96 received first dose of Covishield and Covaxin respectively. Overall, 79.3% showed seropositivity after the first dose. Responder rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (86.8 vs. 43.8%; 61.5 vs. 6 AU/ml; both p<0.001). This difference persisted in propensity-matched (age, sex and BMI) analysis in 172 subjects. No difference was observed with age, gender and BMI. History of hypertension had lower responder rate (65.7 vs. 82.3%, p=0.001). Covishield recipient had more adverse event vs. Covaxin arm (46.7 vs. 31.2%, p=0.006). Presence of comorbidities, past SARS-CoV-2 infection and vaccine types used were independent predictors for seropositivity after the first dose, in multiple logistic regression analysis. ConclusionsWhile both vaccines elicited immune response, seropositivity rates to anti-spike antibody were significantly higher in Covishield recipient compared to Covaxin after the first dose. Ongoing COVAT study will further enlighten the immune response between two vaccines after the second dose. HighlightsO_LIThis study evaluated the humoral antibody response of two SARS-CoV-2 vaccines Covishield and Covaxin in Indian health-care workers. C_LIO_LIBoth vaccines showed seropositivity to anti-spike antibody, 21 days or more after the first dose. C_LIO_LIResponder rates were higher in Covishield recipient compared to Covaxin in propensity-matched cohorts. C_LIO_LIPast SARS-CoV-2 infection, presence of comorbidities and vaccine type received were independent predictors of antibody response after the first dose. C_LI

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9 Citations


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35 results found


Open accessJournal ArticleDOI: 10.1016/S2213-2600(20)30079-5
Xiaobo Yang1, Yuan Yu1, Jiqian Xu1, Huaqing Shu1  +14 moreInstitutions (4)
Abstract: Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

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Topics: Pneumonia (56%), ARDS (55%), Intensive care unit (54%) ... show more

5,846 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2196-X
Roman Wölfel1, Victor M. Corman2, Wolfgang Guggemos, M Seilmaier  +15 moreInstitutions (4)
01 Apr 2020-Nature
Abstract: Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

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Topics: Virus receptor (62%), Coronavirus (60%), Viral shedding (59%) ... show more

4,325 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30185-9
15 Feb 2020-The Lancet
Topics: Coronavirus (65%), Betacoronavirus (55%)

4,001 Citations


Open accessJournal ArticleDOI: 10.1038/S41598-019-56847-4
Ana Rakita1, Nenad Nikolić1, Michael Mildner1, Johannes Matiasek  +1 moreInstitutions (1)
08 Jan 2020-Scientific Reports
Abstract: A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

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Topics: Wound healing (58%), Keratinocyte (57%), Epidermis (botany) (55%) ... show more

2,641 Citations


Open accessJournal ArticleDOI: 10.1093/BIOINFORMATICS/BTY407
James Hadfield1, Colin Megill1, Sidney M Bell2, Sidney M Bell1  +9 moreInstitutions (5)
01 Dec 2018-Bioinformatics
Abstract: Summary Understanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualization platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, open to health professionals, epidemiologists, virologists and the public alike. Availability and implementation All code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.

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1,285 Citations


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