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

Gao, Qiang; Bao, Linlin; Mao, Haiyan; Wang, Lin; Xu, Kangwei; Yang, Mu; Zhu, Ling; Wang, Nan; Lv, Zhe; Gao, Hong; Kan, Biao; Hu, Yaling; Liu, Jiang-ning; Cai, Fang; Jiang, Deyu; Yin, Yanhui; Qin, Cheng‐Feng; Li, Jing; Gong, Xuejie; Fang, Zhiguo; Shi, Wen; Wu, Dongdong; Zhang, Hengming; Zhu, Lang; Deng, Wei; Li, Yurong; Lu, Jinxing; Li, Changgui; Wang, Xiangxi; Yin, Weidong; Zhang, Yanjun; Qin, Chuan

doi:10.1126/science.abc1932

Cited by 1,291 publications

(1,399 citation statements)

References 27 publications

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“…Here, we showed that a single vaccination with ChAdOx1 nCoV-19 is effective in preventing damage to the lungs upon high dose challenge with SARS-CoV-2. Similarly a recent study showed that a triple vaccination regime of a high dose of whole inactivated SARS-CoV-2 protected rhesus macaques from SARS-CoV-2 pneumonia 7 .…”

Section: Discussionmentioning

confidence: 75%

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Doremalen

Lambe

Spencer

et al. 2020

Preprint

262

282

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

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Section: Discussionmentioning

confidence: 75%

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Doremalen

Lambe

Spencer

et al. 2020

Preprint

262

282

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“…We chose to examine beta-propiolactone as a means to inactivate SARS-CoV-2. This method was chosen because it preserves virus structure and antigenicity, and it has recently been used to generate an inactivated vaccine preparation for SARS-CoV-2 [15]. Our data show that treatment of SARS-CoV-2 with beta-propiolactone at a concentration of 0.5% for 16 hours at 4C followed by 2 hours at 37C will yield intact viral particles that can be utilized safely for downstream purposes.…”

Section: Discussionmentioning

confidence: 88%

“…Beta-propiolactone (BPL) is a commonly used reagent for the inactivation of viruses for use in vaccine preparations [11-14] and it has recently been used in the development of an inactivated SARS-CoV-2 vaccine preparation [15]. Our results indicate that incubation of SARS-CoV-2 (×10 6 pfu) in solution with 0.5% BPL for 16 hours at 4C followed by a 2-hour incubation at 37C results in complete inactivation of infectious SARS-CoV-2 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Propagation, inactivation, and safety testing of SARS-CoV-2

Jureka

Silvas

Basler

2020

Preprint

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In late 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-9 CoV-2) emerged in Wuhan, the capital of the Chinese province Hubei. Since then, SARS-CoV-2 has 10 been responsible for a worldwide pandemic resulting in over 4 million infections and over 250,000 11 deaths. The pandemic has instigated widespread research related to SARS-CoV-2 and the disease 12 that it causes, COVID-19. Research into this new virus will be facilitated by the availability of clearly 13 described and effective procedures that enable the propagation and quantification of infectious 14 virus. Because work with the virus is recommended to be performed at biosafety level 3, validated 15 methods to effectively inactivate the virus to enable safe study of RNA, DNA and protein from 16 infected cells are also needed. Here, we report methods used to grow SARS-CoV-2 in multiple cell 17 lines and to measure virus infectivity by plaque assay using either agarose or microcrystalline 18 cellulose as an overlay as well as a SARS-CoV-2 specific focus forming assay. We also demonstrate 19 effective inactivation by TRIzol, 10% neutral buffered formalin, beta propiolactone, and heat. 20 cells to characterize viral genome sequences, monitor viral gene expression and genome replication, 43 and to characterize host responses to infection. Removal of intact, virus-infected cells is critical for 44 studies involving microscopy aimed at understanding the SARS-CoV-2:host interplay at the cellular 45 level, and also for high-throughput analysis of the progression of viral replication in response to 46 antivirals. Whole inactivated virus and viral proteins are needed for the development of inactivated 47 whole-virus vaccine preparations and also as a source of antigen for immunoassays. 48To help address these needs and to facilitate SARS-CoV-2 research efforts, we describe here 49 methods for the propagation of SARS-CoV-2 in multiple cell lines. We have also determined a more 50 efficient method for quantifying virus by plaque assay and have developed a SARS-CoV-2-specific 51 focus forming assay which can enhance throughput of assays requiring quantification of viral titers. 52Additionally, we describe validation if methods for the inactivation of SARS-CoV-2 through the use 53 of TRIzol, 10% neutral buffered formalin, beta-propiolactone, and heat. Taken together, the data 54 presented here will serve to provide researchers with a helpful basis of information to aid in their 55 work on SARS-CoV-2. 56 57 2. Materials and Methods 58 2.1 Cells and Virus 59 60 Vero E6 (ATCC# CRL-1586), Calu-3 (ATCC# HTB-55), Caco-2 (ATCC# HTB-37), Huh7, A549 61 (ATCC# CCL-185), and 293T cells were maintained in DMEM (Corning) supplemented with 10% heat 62 inactivated fetal bovine serum (FBS; GIBCO). Cells were kept in a 37°C, 5% CO2 incubator without 63 antibiotics or antimycotics. SARS-CoV-2, strain USA_WA1/2020, was obtained from the World 64 Reference Collection for Emerging Viruses and Arboviruses at the University of Texas Medical 65 Branch-Galveston. 6...

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“…A safe and effective vaccine is the need of the hour to overcome the COVID-19 pandemic. In the global race for the development of vaccines, few research groups have reported the preclinical studies of viral vector vaccines (ChAdOx1 nCoV-19 and Ad-26.COV.2.S) 4,5 , mRNA vaccine (mRNA-1273) , DNA vaccine (INO-4800) 7 and inactivated vaccines (PiCoVacc and BBIBP-CorV) 8,9 . Phase I/II clinical trial are either completed or on-going for these vaccines.…”

Section: Discussionmentioning

confidence: 99%

Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques

Yadav¹,

Ella²,

Kumar³

et al. 2020

Preprint

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The COVID-19 pandemic is a global health crisis that has severely affected mankind and posed a great challenge to the public health system of affected countries. The availability of a safe and effective vaccine is the need of the hour to overcome this crisis. Here, we have developed and assessed the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in rhesus macaques (Macaca mulata). 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 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 showed features of interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. Data from this study substantiate the immunogenicity of the vaccine candidates and BBV152 is being evaluated in Phase I clinical trials in India (NCT04471519).

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

Cited by 1,291 publications

References 27 publications

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Propagation, inactivation, and safety testing of SARS-CoV-2

Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques

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