On July 20, the results of the Phase I/II clinical trial of the new coronavirus vaccine jointly developed by Oxford University and AstraZeneca and the results of the Phase II clinical trial of CanSino were published in The Lancet at the same time, BioNTech/Pfizer/Fosun The drug's Phase I clinical trial results are pre-released on medRxiv.
Oxford University/AstraZeneca: No early safety concerns, producing a "strong" immune response
According to the official website of Oxford University, the results of the Phase I/II trial published by the Oxford University vaccine team in The Lancet showed that there is no Early safety concerns and elicited strong immune responses in both parts of the immune system. The
vaccine elicits a T-cell response (which attacks white blood cells infected by the SARS-CoV-2 virus) within 14 days of vaccination and an antibody response (antibodies that neutralize the virus so that it does not infect cells during the initial infection) within 28 days. .
During the study, participants who received the vaccine had detectable neutralizing antibodies, which researchers believe are important for protection, and these responses were strongest after a booster dose, with 100% of participants having blood antibodies against the coronavirus Neutralizing activity. The next step in researching this vaccine is to confirm that it is effective in preventing SARS-CoV-2 infection.
“Phase I/II data for our COVID-19 vaccine show that the vaccine did not cause any unexpected reactions and had a similar safety profile to previous vaccines of this type. The immune responses observed after vaccination were consistent with previous animal studies showed an association with protection against the SARS-CoV-2 virus, although we must continue with a rigorous clinical trial program to confirm this in humans," Professor Pollard said. "We found this in 10 participants who received two doses of the vaccine. The strongest immune response was seen, suggesting this could be a good strategy for vaccination."
This Phase I/II trial in the UK began in April to test Oxford's coronavirus vaccine ChAdOx1 nCoV- 19. The team began working on developing a vaccine against the new coronavirus in January 2020.
During Phase I/II, this randomized controlled trial evaluated more than 1,000 healthy adult volunteers aged 18 to 55 years. A subset of these volunteers (10 people) received two doses of the vaccine. A total of 1,077 volunteers received the ChAdOx1 nCoV-19 vaccine or the placebo MenACWY vaccine between April 23, 2020, and May 21, 2020. There were no serious adverse health events related to ChAdOx1 nCoV-19.
According to content released by The Lancet, researchers conducted a Phase 1/2 single-blind, randomized controlled trial in five trial institutions in the UK, using the chimpanzee adenovirus vector vaccine (ChAdOx1 nCoV -19), which expresses SARS-CoV-2 spike protein compared to meningococcal conjugate vaccine (MenACWY) as a control.
Enrollment Healthy adults aged 18–55 years with no history of laboratory-confirmed SARS-CoV-2 infection or COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV- 19 viral particles or MenACWY as a single intramuscular injection. Protocol modifications were made at two of the five sites to allow prophylactic paracetamol to be administered prior to vaccination.
Ten participants assigned to the non-randomized, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose regimen, with a booster vaccine administered 28 days after the first dose. Using a standardized total IgG ELISA against the trimeric SARS-CoV-2 spike protein, a multiplex immunoassay, three real-time SARS-CoV-2 neutralization assays (50% plaque reduction neutralization assay [PRNT 50]), Humoral responses were assessed at baseline and following vaccination. Microneutralization assay [MNA 50, MNA 80 and MNA 90]; and Marburg VN), and pseudovirus neutralization assay. Cellular responses were assessed using an ex vivo interferon-gamma enzyme-linked immunospot assay. The primary outcomes of the
trial are to assess efficacy, assessed by symptomatic virologically confirmed COVID-19 cases, and vaccine safety, assessed by the occurrence of serious adverse events. Secondary outcomes include safety, reactogenicity and immunogenicity of ChAdOx1 nCoV-19, as well as efficacy against hospital-attended COVID-19, death and serum conversion against non-spike proteins. The paper reports preliminary findings on safety, reactogenicity, and cellular and humoral immune responses.
Between April 23 and May 21, 2020, a total of 1077 participants were enrolled and assigned to receive ChAdOx1 nCoV-19 (n = 543) or MenACWY (n = 534), of whom ten participated in non-randomized ChAdOx1 nCoV-19 Prime - Booster Group. In the ChAdOx1 nCoV-19 group, local and systemic reactions were more common, and prophylactic paracetamol use alleviated many local and systemic reactions, including pain, fever, chills, muscle aches, headache, and malaise (all p
in In the ChAdOx1 nCoV-19 group, spike-specific T cell responses peaked on day 14. Anti-peak IgG responses increased by day 28 and increased after the second booster dose in all participants. Possessing neutralizing activity. Neutralizing antibody responses were highly correlated with antibody levels measured by ELISA.
showed that ChAdOx1 nCoV-19 exhibited acceptable safety, and the researchers concluded that "these are encouraging. The results support further evaluation of this vaccine candidate in our ongoing large-scale Phase III program, which remains necessary to assess the vaccine's ability to protect people from COVID-19 infection."
The University of Oxford is working with UK-based Global. The government has given a further £84 million to plans to partner with biopharmaceutical company AstraZeneca to further develop, mass-produce and potentially distribute the Covid-19 vaccine, as well as the global clinical development and production of the Oxford vaccine. The program was developed to help accelerate vaccine development.
AstraZeneca Executive Vice President Mene Pangalos said, "We are encouraged by the interim Phase I/II data showing that AZD1222 is able to generate rapid antibodies against SARS-CoV-2. and T cell responses, although more work remains to be done, today's data increases our confidence that the vaccine will work and allows us to proceed with plans to produce the vaccine at scale for widespread, equitable distribution around the world. "
The University of Oxford and AstraZeneca are working with clinical partners around the world as part of a global clinical program to trial the Oxford vaccine. The global program consists of a Phase III clinical trial enrolling 30,000 patients in the United States. , a pediatric study, and a Phase III clinical trial already underway in low- and middle-income countries, including Brazil and South Africa.
If late-stage clinical trials prove successful, AstraZeneca will continue to fulfill its commitment to broad and Commitments for equitable access to vaccines. So far, commitments have been made with the UK, the US, Europe's IVA, CEPI, Gavi and the Serum Institute of India to provide more than 2 billion doses of vaccine.
Chen Wei. team/CanSino: After a single shot of immunization, the vast majority of subjects stimulated significant immune responses
The paper is titled "Immunogenicity and safety of recombinant novel coronavirus vaccine (adenoviral vector) in healthy adults aged 18 years and older: a randomized, double-blind, placebo-controlled phase II trial", which It is the first phase II randomized controlled trial to evaluate the immunogenicity and safety of a recombinant new coronavirus vaccine (adenoviral vector), with the purpose of determining a suitable dose and conducting an effectiveness study.
This is a single-center randomized, double-blind, placebo-controlled Phase 2 clinical trial of a recombinant novel coronavirus vaccine (adenoviral vector) conducted in Wuhan, China. The subjects were healthy adults aged 18 and above, with negative HIV test results and no SARS-CoV-2 infection. Recruited eligible subjects were randomly assigned to a 1×1011 virus particle dose group, a 5×1010 virus particle dose group, or a placebo group. Researchers allocated subjects in a 2:1:1 (medium dose, low dose, placebo) ratio, and a randomization list (segment length 4) was generated by an independent statistician. The subject received a single injection of vaccine into the arm muscle. Participants, investigators, and laboratory analysis staff performed the study in a blinded manner.The main immunogenicity indicator is the geometric mean titer (GMT) of the antibody Receptor Binding Domain (RBD) detected by enzyme-linked ELISA method at 28 days, and the main safety indicator is the adverse reactions occurring within 14 days. All subjects who participated in this clinical trial (received one dose) were included in the primary and secondary safety analyses. The trial is registered with ClinicalTrials.gov, registration number NCT04341389.
The trial recruited 603 volunteers and conducted rigorous screening between April 11, 2020, and April 16, 2020. 508 eligible subjects (50% male, mean age 39.7 years, SD 12.5) agreed to participate in the clinical trial and were randomly assigned to vaccine groups (1 × 1011 virus particle dose group, 253 and 5 × 1010 virus particle dose group) , 129 people), or the placebo group (126 people). In the vaccine 1×1011 virus particle dose and 5×1010 virus particle dose groups, the peak RBD-specific ELISA antibody titers at 28 days were 656.5 (95% CI, 575.2-749.2) and 571.0 (95% CI, 467.6-697.3), and the seroconversion rates were 96% (95% CI, 93%-98%) and 97% (92%-99%) respectively. Both dose groups induced significant neutralizing antibody responses to neutralize SARS-CoV-2, with GMTs of 19.5 (95% CI, 16.8-22.7) and 5×1010 VP dose groups, respectively. 18·3 (95% CI, 14.4-23.3). 227 of 253, or 90% (95% CI, 85%-93%) patients in the 1×10 virus particle dose group, and 113 of 129, or 88%, of the 5×10 virus particle dose group. (95% CI, 81%-92%) Specific positive interferon-gamma ELISpot results were observed. Serious adverse events occurred in 24 people (9%) and 1 person (1%) in the 1×1011 and 5×1010 virus particle dose groups respectively; however, no serious adverse reactions occurred in the entire clinical trial. The
recombinant novel coronavirus vaccine (adenoviral vector) is safe at a dose of 5×1010 viral particles per dose. After a single injection of immunization, a significant immune response was stimulated in the vast majority of subjects.
Ad5-nCoV was jointly developed by CanSino and the Institute of Bioengineering, Academy of Military Medicine, Academy of Military Sciences. Ad5-nCoV is constructed using genetic engineering methods, using replication-deficient human adenovirus type 5 as a vector, which can express the S antigen of the new coronavirus and is intended to be used to prevent diseases caused by new coronavirus infection.
BioNTech/Pfizer: Stimulate antibody and T cell responses at very low dose levels
html On July 20, the mRNA new crown vaccine BNT162b1 jointly developed by BioNTech and Pfizer (and Fosun Pharmaceutical) released new progress: 1/ Preliminary data from a Phase 2, open-label, non-randomized, non-placebo-controlled, dose-escalation trial. Previously, the two companies had announced preliminary data from clinical trials of the vaccine in the United States. The trial is part of a global program for mRNA-based vaccines. The data are available on medrxiv's online preprint server and are currently undergoing scientific peer review for potential publication.
Preliminary clinical results are for the most advanced investigational vaccine in Pfizer and BioNTech's BNT162 mRNA-based vaccine program against SARS-CoV-2, BNT162b1. The vaccine candidate is a lipid nanoparticle-formulated, nucleoside-modified messenger RNA encoding an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen. Overall, the new preliminary data from the German study support and extend the recently published early results from the corresponding U.S. BNT162b1 trial.
Preliminary data on BNT162b1 were evaluated in a German Phase 1/2 clinical trial involving 60 healthy adults aged 18 to 55 years. Of these 60 participants, 12 subjects at each dose level (1 µg, 10 µg, 30 µg, and 50 µg; 48 total participants) received vaccine with BNT162b1 on Days 1 and 22 vaccination (n = 12 per primary booster group), n = 11 for the 10 µg and 50 µg cohorts from day 22 onwards. In addition, 12 participants received a single injection of 60 µg.
After the second injection, the vaccine induced high dose-dependent SARS-CoV-2 neutralizing titers and RBD-binding IgG concentrations. Day 43 SARS-CoV-2 neutralizing geometric mean titers ranged from 0.7-fold (1 μg) to 3.2-fold (50 μg) compared with a panel of convalescent SARS-CoV-2-infected human sera.Furthermore, in a panel of sixteen SARS-CoV-2 RBD variants represented by publicly available SARS-CoV-2 sequences and against the newly dominant D614G strain, in a pseudovirus neutralization assay, vaccinated The subjects' sera showed broad neutralizing activity.
Additionally, preliminary trial results in Germany demonstrate for the first time that the BNT62b1 drug candidate induces both high-level CD4+ and CD8+ T-cell responses against the SARS-CoV-2 RBD.
The strength of the T-cell response varied from subject to subject. There was no clear dose level dependence of T cell responses between 1 µg and 50 µg, indicating that stimulation and robust expansion of T cells can be achieved at low mRNA dose levels.
All subjects in the prime-boost cohort, except two subjects at the lowest dose level, had CD4+ T cell responses. Cytokine analysis of RBD-specific CD4+ T cells revealed T H 1 dominance of these cells. Of the 36 subjects tested, 29 also had RBD-specific functional CD8+ T cell responses that were comparable to memory responses against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and influenza viruses .
Overall, the data indicate that BNT162b1 can be administered safely and has a manageable tolerability profile. Following injection of BNT162b1 at all dose levels, local reactions and systemic events were transient and generally mild to moderate, with occasional severe influenza-like symptoms and injection site reactions (Grade 3). All adverse events resolved spontaneously and were managed with simple measures. No serious adverse events (SAEs) were reported and there were no discontinuations due to vaccine-related adverse events. Özlem Türeci, co-founder of
BioNTech, said, "It is encouraging that the BNT162b1 data from the German study cohort is very consistent with what we have seen in the U.S. study cohort. Preliminary data shows that our mRNA-based vaccine can be used at very low dose levels Stimulating antibody as well as T cell responses. We believe both may play an important role in the effective clearance of pathogens such as SARS-CoV-2. "
" These interim results from the German study, combined with preliminary data from the US study, highlight that "We remain committed to developing effective vaccines," said Kathrin U. Jansen, senior vice president and head of vaccine development at Pfizer. vaccine to combat the COVID-19 pandemic and prioritize safety, and look forward to sharing more data as the program progresses."
The companies said they will use preliminary data from Phase 1/2 studies in Germany and the United States, as well as Additional preclinical and clinical data are being generated to determine dose levels and select among multiple vaccine candidates as we seek to advance them to anticipated high-dose, global Phase 2b/3 safety and efficacy trials. The trial could involve up to 30,000 healthy participants and, subject to regulatory approval, is expected to begin in late July 2020. The
BNT162b1 drug candidate remains in clinical studies and is not currently approved for release anywhere in the world. If ongoing studies are successful and the vaccine candidate receives regulatory approval, the companies expect to produce up to 100 million doses by the end of 2020 and potentially more than 1.3 billion doses by the end of 2021. In this case, BioNTech and Pfizer will work together to distribute a potential COVID-19 vaccine globally (except in China, where BioNTech collaborates with Fosun Pharma on BNT162 for clinical development and commercialization).
Clinical trials of the vaccine have just started in China. On July 16, Fosun Pharma announced that the vaccine had been approved for clinical trials by the National Medical Products Administration. On July 18, the Phase I clinical trial launch and training meeting for the new coronavirus mRNA vaccine (BNT162b1) authorized by BioNTech to Fosun was held on July 18 at the China Medical City in Taizhou, Jiangsu Province, and volunteers are being recruited.
In March 2020, Fosun Pharma was authorized by Germany's BioNTech to exclusively develop and commercialize vaccine products against the new coronavirus based on its proprietary mRNA technology platform in mainland China, Hong Kong, Macao and Taiwan (the same below). The vaccine is a preventive biological product and is intended to be mainly used for people aged 18 and above to prevent novel coronavirus infection.According to the latest public information from BioNTech, its mRNA-based new coronavirus vaccine has achieved positive results in Phase 1/2 clinical trials. Among them, the two most advanced mRNA-based vaccine candidates, BNT162b1 and BNT162b2, have recently received fast track qualifications from the US FDA. (Fast Track designation).
This phase I clinical trial is conducted by Jiangsu Provincial Center for Disease Control and Prevention ( Jiangsu Provincial Institute of Public Health ). The trial site is located at Taizhou China Medical City Vaccine Engineering Center, Taizhou City Center for Disease Control and Prevention , Taizhou People's Hospital and other units participated.
According to the announcement issued by Fosun Pharma, the study plans to recruit 100 people aged 18-55 years old and 140 people aged 55 and above. The plan is to recruit healthy adults aged 18 and above, hold Jiangsu "Sukang Code" or "Xiangtai Code" green code, have no history of vaccination allergies, no history of COVID-19 pneumonia or infection, and can persist in completing 12 months Study follow-up. Only open to permanent residents of Taizhou and surrounding areas, with priority given to residents surrounding China Medical City. The
research team will conduct a preliminary screening based on the content filled in the "New Crown Vaccine Clinical Research Appointment Registration and Active Health Declaration System" and notify qualified volunteers by phone to come to the Vaccine Engineering Center of Taizhou China Medical City (28 Xinglin Road, Taizhou Medical City No. 1, Building B, Vaccine Engineering Center) for further physical examination, and those who pass the test will be selected.
"We will collect blood samples from volunteers 10 times: physical examination the day before vaccination and the day of vaccination (day 1), day 2 after vaccination, day 8 after vaccination, day 22 after vaccination, and day 29 after vaccination , the 43rd day after vaccination, the 3rd month after vaccination, the 6th month after vaccination, and the 12th month after vaccination, a total of 316ml of blood was collected on the day of vaccination, the 29th day after vaccination, and the 43rd day after vaccination. A nutrition and transportation subsidy of 1,200 yuan will be provided, and a nutrition and transportation subsidy of 800 yuan will be given each time for the remaining 7 times (similar studies in the United States are US$100/time), and three times on the 15th day after vaccination, the 36th day after vaccination, and the 50th day after vaccination. A transportation subsidy of 200 yuan will be provided for each safety visit. Those who complete 13 visits and 10 samplings will receive a maximum compensation of 9,800 yuan. For more information, please download 21 Finance APP
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