Covid-19 vaccine: 81% of the clinical trial volunteers had reactions to the vaccine
Vaccine that uses HEK293 human fetal cell lines
by Marco Cáceres and Barbara Loe Fisher
Posted on 6 July 2020 | Vaccination, Risk & Failure Reports
An experimental vaccine for COVID-19 has been developed by CanSino Biologics, Inc. of Tianjin, China, in collaboration with the Institute of China's Academy of Military Medical Sciences' Institute of Biotechnology. A Phase 1 human clinical trial of the COVID-19 vaccine (adenovirus type-5 Ad5-nCoV) has been completed in China with 108 volunteers, aged between 45 and 60. (1 2 3 4)
In that trial, 87 (81 percent) of the 108 participants experienced at least one adverse reaction within seven days of vaccination. Of these, 30 participants were in the low-dose group, 30 were in the medium-dose group, and 27 were in the high-dose group. Overall, 10 of the participants had grade 3 adverse reactions. Of the 36 participants in the high-dose group, six of them had grade 3 adverse reactions. (1 2)
Pain, fever, fatigue, headache among the most common reactions to the CanSino Ad5-nCoV vaccine for COVID-19.
According to the researchers who conducted the Phase 1 clinical trial study for the Ad5-nCoV vaccine: the most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients. Pain was reported in 17 (47%) participants in the low dose group, 20 (56%) participants in the medium dose group, and 21 (58%) participants in the high dose group. The most commonly reported systemic adverse reactions were overall fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]) and muscle pain (18 [17%]). Fever was reported in 15 (42%) participants in the low dose group, 15 (42%) participants in the medium dose group, and 20 (56%) participants in the high dose group. Headache was reported in 14 (39%) participants in the low dose group, 11 (31%) participants in the medium dose group, and 17 (47%) participants in the high dose group. Muscle pain was reported in 7 (19%) participants in the low dose group, 3 (8%) participants in the medium dose group and eight (22%) participants in the high dose group. (2)
Nine of the participants, including two in the low-dose group, two in the medium-dose group and five in the high-dose group, developed grade 3 fevers of over 101,3 ° F (38.5 ° C). One of the participants in the high-dose group reported "severe fever along with severe symptoms of fatigue, wheezing and muscle pain". Another participant in the high-dose group experienced "severe fatigue and joint pain". The reactions occurred within 24 hours of vaccination. (1 2)
Experimental trials of COVID-1273's Modern mRNA-19 COVID-19 also recorded grade 3 reactions.
As in the CanSino Phase 5 Ad1-nCov vaccine trial, some participants in the Phase 1 mRNA-1273 COVID-19 vaccine trial conducted by Moderna, Inc. also experienced Grade 3 reactions earlier this year. Of the 45 volunteers who participated in the Moderna clinical trial during the March-May 2020 period, nine percent of them had serious adverse reactions to the mRNA-1273 vaccine, including 29-year-old Ian Haydon from Seattle, Washington. (1 2) Haydon underwent Grade 3 reactions twelve hours after obtaining the second of two 250 µg doses of the mRNA-1273 vaccine. He developed a fever of over 103 degrees (39.5 C °) and eventually passed out. (1 2) Grade 3 reactions are described by the United States Department of Health and Human Services (HHS) as "serious or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization; disabling; which limits being able to take care of oneself "like" bathing, getting dressed and undressing, feeding, using the toilet, taking drugs ". The only thing worse than Grade 3 events are those classified as Grade 4, which is "life threatening" and "Grade 5, which is" death ". (5 6 7)
CanSino reported entering Phase 2 of the human clinical trial on the Ad5-nCoV vaccine for COVID-19.
Reportedly, CanSino Biologics has started a Phase 2 human clinical trial of the Ad5-nCoV vaccine using the HEK293 cell line which provides testing on 500 healthy volunteers. On May 12, the National Research Council of Canada (NRC) announced a collaboration agreement with the Chinese company to "advance biotreatment and clinical development in Canada" for the Ad5-nCoV vaccine. (4 8 9 10) In a press release, the NRC said: "This partnership will allow the NRC to advance a scale-up (high-level) production process for the candidate vaccine, using its proprietary cell line. HEK293 "(9 10) To facilitate this work, the Canadian government has announced that it will provide $ 44 million to upgrade Montreal's NRC facilities to" enable compliance with Good Manufacturing Practice (GMP) standards "and to" ensure the availability of potential vaccine candidates for Canadian biotreatment as soon as they become available "(9). "It's the perfect time to take advantage of the cutting-edge technology and resources of both sides that are critical to Ad5-nCoV's development," said Xuefeng Yu, CEO of CanSino Biologics. (10)
The CanSino Ad5-n-CoV vaccine uses human fetal cell lines HEK-293 for production.
Life Site News reported on June 26, 2020 that CanSino's Ad5-n-CoV vaccine uses a chimpanzee adenovirus vector that uses HEK293 cell lines derived from the tissue of an aborted fetus. (11) The human fetal cell line HEK293, which It was designed, developed and authorized by the National Research Council of Canada (NRC), it is also used to produce the AZD1222 COVID-19 vaccine developed by the Jenner Institute of the University of Oxford. The joint May 12, 2020 press release issued by the Canadian NRC and CanSino Biologics, Inc. said: "The relationship between the NRC and CanSinoBIO was first established in 2013. The NRC's HEK293 cell line was subsequently licensed to CanSinoBIO and used for the development of an approved vaccine against the Ebola virus "(12).
According to News Medical:
The HEK293 cell line was initially produced in 1973 by a team led by Alex van der Eb in Leiden (the Netherlands) from normal fetal embryonic human kidney cells. These cells were created following a transfection with the cut DNA 5 adenovirus, which led to the incorporation of part of the adenoviral genome into human chromosome 19 of the fetal cell genome. The name 293 derives from the fact that it was the 293rd experiment of Frank Graham (one of van de Eb's postdoctorates). These cells were initially thought to originate from an endothelial, epithelial, or fibroblastic cell from the fetal kidney. However, recent evidence in the cellular characteristics of HEK293 cells has led to the suggestion that they may actually come from a fetal kidney neuronal cell. Following sequencing studies, it has also been identified that these cells have a very complicated karyotype, with multiple copies of chromosomes. For example, these cells have four copies of chromosome 17. It has also been established that these cells do not have a single Y chromosome, but have three X chromosomes, which suggests that the fetus from which they were obtained is a female. (13)
The HEK293 cell is described by Creative Biolabs in this way:
The Human Embryonic Kidney 293 (HEK293) cell line is a predominant host for both stable and transient expression of proteins of varying degrees of research and therapeutic proteins, and more recently, five therapeutic agents produced in HEK293 cells are have been approved by the FDA or the European Medicines Agency (EMA) for therapeutic use. Since it was generated more than 40 years ago, the HEK293 cell line has been used extensively as a robust and reliable platform to produce a lot of recombinant antibodies, antibody fusion proteins and proteins important for the neuropharmacologist, such as paired receptors of the G protein, ligand-gated ion channels and voltage sensitive (voltage) ion channels. The HEK293 cell line was originally generated by the transformation of normal human embryonic kidney (HEK) cells after exposure to cut fragments of human adenovirus type 5 (Ad5) of DNA. The adenovirus E1A gene is expressed in these cells and participates in the transactivation of some viral promoters, allowing these cells to produce very high levels of proteins. (14)
- Branswell H. Early study of Covid-19 vaccine developed in China sees mixed results. STAT May 22, 2020.
- Hou LH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomized, first-in-human trial. The Lancet June 13, 2020; 395 (10240): 1845-1854.
- Liu A. China's CanSino Bio advances COVID-19 vaccine into phase 2 on preliminary safety data. Fierce Pharma Apr. 10, 2020.
- US Food and Drug Administration. Cansino Biologics Moves COVID-19 Vaccine Candidate Into Phase 2 Trial. FDA News Apr. 14, 2020.
- Cáceres M. Healthy Clinical Trial Subjects Suffer Grade 3 Side Effects to Moderna's mRNA COVID-19 Vaccine. The Vaccine Reaction May 24, 2020.
- Cáceres M. Volunteer Describes His Serious Reaction in Moderna's mRNA COVID-19 Vaccine Trial. The Vaccine Reaction May 30, 2020.
- US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Nov. 27, 2017.
- Rettner R. Coronavirus vaccine developed in China shows promise after early study in 100 people. Fox News May 27, 2020.
- Press Release. The National Research Council of Canada and CanSino Biologics Inc. announce collaboration to advance vaccine against COVID-19. National Research Council of Canada May 12, 2020.
- Dearment A. CanSino Biologics may start clinical development of Covid-19 vaccines in Canada. MedCity News May 13, 2020.
- Murdoch A. UK university test COVID-19 vaccine derived from aborted fetal cell line in Africa, Brazil. Life Site News June 26, 2020.
- Bloomberg. NRC of Canada and CanSino Biologics, Inc. announce collaboration to advance vaccine against COVID-19. May 12, 2020.
- Simmons H. HEK293 Cells: Applications and Advantages. News Medical Jan. 8, 2019.
- Creative Biolabs. HEK293 Cell Lines 2020.
Translation by Giulia G.