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1.
Am J Infect Control ; 50(3): 319-324, 2022 03.
Article in English | MEDLINE | ID: covidwho-1694005

ABSTRACT

BACKGROUND: The recent COVID-19 pandemic highlights the need for efficacious virucidal products to limit the spread of SARS-CoV-2. Several studies have suggested that alcohol-based sanitizers and some disinfectants are effective. While virucidal activity data of low-level disinfectants are lacking and some conclusions are not clear yet. METHODS: We evaluated the virucidal activity of 2 quaternary ammonium compounds (QAC) disinfectants (MICRO-CHEM PLUS and FWD), W30 (an amphoteric surfactant), and Medical EtOH against SARS-CoV-2. Suspension tests covering different concentration and contact time were performed using the integrated cell culture-qPCR method. RESULTS: Each of disinfectants was effective at inactivating SARS-CoV-2. MCP and FWD are highly effective within 15 seconds. W30 is also efficient within 2 minutes at concentration of 1%. Consistent with previous report, our results also demonstrated that 38% ethanol was sufficient to completely inactivate virus, which proved the method used in this study is feasible. CONCLUSIONS AND DISCUSSION: QAC disinfectants, MCP and FWD, are highly effective for the inactivation of SARS-CoV-2, which making them practical for use in health care setting and laboratories where prompt disinfection is important. The low-level disinfectant based on amphoteric surfactant, W30, which may present in commonly available household hygiene agents is also able to inactivate SARS-CoV-2.


Subject(s)
COVID-19 , Disinfectants , COVID-19/prevention & control , Disinfectants/pharmacology , Disinfection/methods , Humans , Pandemics , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311717

ABSTRACT

The Coronavirus Disease of 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health and economy. Therapeutic options such as monoclonal antibodies (mAbs) against SARS-CoV-2 are in urgent need. We have identified potent monoclonal antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients and one of these antibodies, P4A1, interacts directly and covers the majority of the Receptor Binding Motif (RBM) of Spike receptor-binding domain (RBD), shown by high-resolution complex structure analysis. We further demonstrated P4A1 binding and neutralizing activities against wild type and mutant spike proteins. P4A1 was subsequently engineered to reduce the potential risk for antibody-dependent enhancement (ADE) of infection and to extend its half-life. The engineered mAb exhibits optimized pharmacokinetic and safety profile, and results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection.

5.
Am J Infect Control ; 50(3): 319-324, 2022 03.
Article in English | MEDLINE | ID: covidwho-1509486

ABSTRACT

BACKGROUND: The recent COVID-19 pandemic highlights the need for efficacious virucidal products to limit the spread of SARS-CoV-2. Several studies have suggested that alcohol-based sanitizers and some disinfectants are effective. While virucidal activity data of low-level disinfectants are lacking and some conclusions are not clear yet. METHODS: We evaluated the virucidal activity of 2 quaternary ammonium compounds (QAC) disinfectants (MICRO-CHEM PLUS and FWD), W30 (an amphoteric surfactant), and Medical EtOH against SARS-CoV-2. Suspension tests covering different concentration and contact time were performed using the integrated cell culture-qPCR method. RESULTS: Each of disinfectants was effective at inactivating SARS-CoV-2. MCP and FWD are highly effective within 15 seconds. W30 is also efficient within 2 minutes at concentration of 1%. Consistent with previous report, our results also demonstrated that 38% ethanol was sufficient to completely inactivate virus, which proved the method used in this study is feasible. CONCLUSIONS AND DISCUSSION: QAC disinfectants, MCP and FWD, are highly effective for the inactivation of SARS-CoV-2, which making them practical for use in health care setting and laboratories where prompt disinfection is important. The low-level disinfectant based on amphoteric surfactant, W30, which may present in commonly available household hygiene agents is also able to inactivate SARS-CoV-2.


Subject(s)
COVID-19 , Disinfectants , COVID-19/prevention & control , Disinfectants/pharmacology , Disinfection/methods , Humans , Pandemics , SARS-CoV-2
6.
Cell Discov ; 7(1): 82, 2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1397862

ABSTRACT

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate. Formulated with aluminum adjuvant, RBD dimer elicited strong immune response in both rodents and non-human primates, and protected mice from SARS-CoV-2 challenge with significantly reducing viral load and alleviating pathological injury in the lung. In the non-human primates, the vaccine could prevent majority of the animals from SARS-CoV-2 infection in the respiratory tract and reduce lung damage. In addition, antibodies elicited by this vaccine candidate showed cross-neutralization activities to SARS-CoV-2 variants. Furthermore, with our expression system, we provided a high-yield RBD homodimer vaccine without additional biosafety or special transport device supports. Thus, it may serve as a safe, effective, and low-cost SARS-CoV-2 vaccine candidate.

7.
Signal Transduct Target Ther ; 5(1): 218, 2020 10 03.
Article in English | MEDLINE | ID: covidwho-1387198

Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Cardiac Glycosides/pharmacology , Gene Expression Regulation/drug effects , Host-Pathogen Interactions/drug effects , Animals , Antiviral Agents/chemistry , Betacoronavirus/pathogenicity , Biological Products/chemistry , Biological Products/pharmacology , Bufanolides/chemistry , Bufanolides/pharmacology , COVID-19 , Cardiac Glycosides/chemistry , Cell Survival/drug effects , Chlorocebus aethiops , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Digoxin/chemistry , Digoxin/pharmacology , High-Throughput Screening Assays , Host-Pathogen Interactions/genetics , Humans , Janus Kinases/antagonists & inhibitors , Janus Kinases/genetics , Janus Kinases/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , NF-kappa B/metabolism , Pandemics , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Signal Transduction , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Sodium-Potassium-Exchanging ATPase/genetics , Sodium-Potassium-Exchanging ATPase/metabolism , Vero Cells , Virus Replication/drug effects
9.
EClinicalMedicine ; 38: 101010, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1300745

ABSTRACT

BACKGROUND: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years. METHODS: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants (n = 336 in 18-59 age group and n = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809. FINDINGS: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups. INTERPRETATION: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.

10.
MAbs ; 13(1): 1930636, 2021.
Article in English | MEDLINE | ID: covidwho-1258715

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antibodies, Neutralizing/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/prevention & control , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibody Specificity , Binding Sites, Antibody , CHO Cells , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Chlorocebus aethiops , Cricetulus , Disease Models, Animal , Epitopes , Macaca mulatta , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vero Cells
11.
J Environ Sci (China) ; 112: 115-120, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1230607

ABSTRACT

Wastewater-based epidemiology (WBE) has emerged as an effective environmental surveillance tool in monitoring fecal-oral pathogen infections within a community. Congruently, SARS-CoV-2, the etiologic agent of COVID-19, has been demonstrated to infect the gastrointestinal tissues, and be shed in feces. In the present study, SARS-CoV-2 RNA was concentrated from wastewater, sludge, surface water, ground water, sediment, and soil samples of municipal and hospital wastewater systems and related environments in Wuhan during the COVID-19 middle and low risk periods, and the viral RNA copies quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). From the findings of this study, during the middle risk period, one influent sample and three secondary effluents collected from waste water treatment plant 2, as well as two samples from Jinyintan Hospital wastewater system influent were SARS-CoV-2 RNA positive. One sludge sample collected from Guanggu Branch of Tongji Hospital, which was obtained during the low risk period, was also positive for SARS-CoV-2 RNA. These study findings demonstrate the significance of WBE in continuous surveillance of SARS-CoV-2 at the community level, even when the COVID-19 prevalence is low. Overall, this study can be used as an important reference for contingency management of wastewater treatment plants and COVID-19 prevention and control departments of Wuhan.


Subject(s)
COVID-19 , Waste Water , Environmental Monitoring , Humans , RNA, Viral , SARS-CoV-2
12.
Nat Commun ; 12(1): 2623, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225506

ABSTRACT

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antibody Specificity/immunology , COVID-19/drug therapy , COVID-19/epidemiology , Cell Line, Tumor , Cells, Cultured , Chlorocebus aethiops , Female , Humans , Macaca mulatta , Male , Mutation , Pandemics , Protein Binding , Protein Domains , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Treatment Outcome , Vero Cells
13.
Virol Sin ; 36(5): 879-889, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1174014

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , Mice , Mice, Transgenic , Primates , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Inactivated/immunology
14.
Emerg Microbes Infect ; 9(1): 2653-2662, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-977352

ABSTRACT

In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.


Subject(s)
COVID-19 Vaccines , Protein Processing, Post-Translational , SARS-CoV-2/isolation & purification , Viral Structural Proteins , Virion , Animals , Antigens, Viral/analysis , Antigens, Viral/metabolism , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Cattle , Chlorocebus aethiops , Humans , Rabbits , SARS-CoV-2/immunology , Vaccines, Inactivated/chemistry , Vaccines, Inactivated/immunology , Vero Cells , Viral Structural Proteins/chemistry , Viral Structural Proteins/immunology , Viral Structural Proteins/isolation & purification , Virion/chemistry , Virion/immunology , Virion/isolation & purification
16.
Emerg Microbes Infect ; 9(1): 2606-2618, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-944152

ABSTRACT

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2 , Animals , Antibodies, Viral , COVID-19 Vaccines/adverse effects , Female , Immunity, Humoral , Male , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology
17.
Nat Commun ; 11(1): 5752, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-926678

ABSTRACT

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Viral/immunology , COVID-19 , Cell Line , Chlorocebus aethiops , Coronavirus Infections/prevention & control , Female , HEK293 Cells , Humans , Macaca mulatta , Male , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/prevention & control , Receptors, IgG/genetics , Receptors, IgG/immunology , Receptors, Virus/metabolism , SARS-CoV-2 , Vero Cells , Virus Attachment
18.
JAMA ; 324(10): 951-960, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-911581

ABSTRACT

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Adolescent , Adult , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/adverse effects , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/genetics , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Dose-Response Relationship, Immunologic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Pneumonia, Viral/immunology , Propiolactone , SARS-CoV-2 , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
20.
Nat Commun ; 11(1): 4207, 2020 08 21.
Article in English | MEDLINE | ID: covidwho-724410

ABSTRACT

The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1 × 1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/administration & dosage , Adenoviridae/genetics , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Dose-Response Relationship, Immunologic , Female , HEK293 Cells , Humans , Immunity, Cellular , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Pneumonia, Viral/immunology , Respiratory System/pathology , Respiratory System/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/administration & dosage
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