Under normal circumstances, the birth of a vaccine usually takes 7 to 12 years; now, within 8 months, many new crown vaccines have gone It’s phase III. Will this become a template for changing the development of vaccines for emergent infectious diseases in the future? This article is from the WeChat official account: China News Weekly (ID: chinanewsweekly) , author: Peng Danni, editor: Xiao Ran, title Picture from: Visual China
Global competition for the development of new crown vaccine
In 2009, at a family gathering in a spacious backyard in Toronto, Canada, a group of Chinese vaccine experts with senior positions in multinational pharmaceutical companies talked about the vaccine problem that China has long lagging behind developed countries. This year, four of them left Canada and returned to Tianjin, China to establish CanSino. Due to the close relationship with Canada, the company’s English name (CanSino) is a joint written by Canada and China.
However, in addition to an Ebola vaccine developed in cooperation with the Chen Wei team of the Chinese Academy of Military Sciences as a national emergency reserve, it was granted conditional marketing approval in 2017. So far, although this vaccine company has 16 vaccines in Research, but there is still no product on the market, with a cumulative loss of about 470 million yuan. Now, relying on a new crown vaccine developed in cooperation with Chen Wei’s team again, on August 13, Cansino was listed for trading on the Science and Technology Innovation Board, with a market value of over 100 billion yuan, and it has become the domestic “first new crown vaccine.”
The four giants of global vaccines are GlaxoSmithKline in the United Kingdom, Pfizer and Merck in the United States, and Sanofi Pasteur in France. They account for 90% of the global vaccine market. At the beginning of the new crown epidemic, they did not actively participate. Vaccine research and development is an industry that requires huge capital and is full of uncertainty.
But this does not preventmore and more vaccine manufacturers, biotech companies and scientists are investing in.Issues such as vaccine production in clinical trials. On June 4, the vaccine recruited participants to enter the Phase III trial, including 10,000 participants from the United Kingdom and 30,000 participants recruited by AstraZeneca in the United States. On June 2, Brazil also approved the vaccine for local clinical trials. The trial plans to include 2,000 volunteers.
This vaccine became the first one in the world to enter Phase II/III clinical trials. It is late July that the inactivated vaccine from China Kexing and the two mRNA vaccines from the United States announced that they will enter Phase III. Until August 9, Saudi Arabia announced that it will cooperate with Cansino to launch a phase III clinical trial of the adenovirus vaccine, and it plans to recruit 5,000 subjects. On August 17, Pakistan stated that it would also conduct phase III clinical trials of Cansino vaccine. In addition, Cansino also launched Phase III in Russia on August 14.
Sarah Gilbert, the head of Oxford Vaccine Research and Development, has great confidence in her vaccine. In an interview with Bloomberg Businessweek, she believes that the Oxford vaccine has an 80% chance of effectively preventing vaccinators from contracting the new coronavirus, and this result will be announced in September. She said: “We know the circumstances of the adverse event, we know the dose that needs to be used, because we have done it many times.”
However, on September 8, AstraZeneca announced that it would voluntarily suspend the phase III clinical trial of the new crown vaccine in cooperation with the University of Oxford and accept the review of safety data by an independent committee because of a British subject Suspected serious adverse reactions occurred.
AstraZeneca said in a statement, “This suspension is a routine action. As long as an unexplained underlying disease appears in a trial, such action must be taken during the investigation. , To ensure that the integrity of the trial is maintained.” It also stated that it is working hard to expedite the review of this single incident to minimize any potential impact on the trial schedule.
Whether the adverse event was caused by the vaccine or the subject is still subject to investigation. Qin Yuan believes that if there are serious adverse reactions such as 5% to 10%, it means that the vaccine does have safety problems, but this case is only present, and it is likely to be an accident. “I think the vaccine will restart (Phase III clinical trial) after objective evaluation.”
A person familiar with the matter said in an interview with the American medical media STAT that the volunteer is expected to recover. But it is still unclear about the nature and time of its adverse reactions. Also on this day, AstraZeneca, BioNTech, Moderna, Pfizer, etc.The 100 microgram dose group was 339.7 and 654.3 respectively. On August 12, the mRNA vaccine jointly developed by German biotechnology company BioNTech and Pfizer of the United States also published its Phase I/II clinical trial data in the journal Nature. Volunteers vaccinated with doses of 10 micrograms and 30 micrograms of vaccine had their average titers of neutralizing antibodies peaking at 168 and 267 on the 7th day after the second vaccination.
On July 20th, two adenovirus vector vaccines are catching up step by step: Chen Wei’s team’s type 5 adenovirus vaccine(Ad5-nCoV)Phase II clinical trial data and the Phase I/II clinical trial data of the chimpanzee adenovirus new crown vaccine co-operated by Oxford University and AstraZeneca were published in The Lancet.
In the neutralization test of the Oxford University vaccine that can reduce the infection rate of the new coronavirus by 50%, the subjects all activated the neutralizing antibody at 28 days of vaccination, with an average titer of 218. However, in the phase II clinical trial, the average titers of neutralizing antibodies in the high-dose and low-dose groups of the Chen Wei team vaccine were 19.5 and 18.3, respectively. Similar to the results of Phase I: 28 days after vaccination, the levels of activated neutralizing antibodies in each dose group did not exceed 40.
In general, these vaccines have activated antibodies, especially neutralizing antibodies, 2 to 4 weeks after vaccination. But experts emphasize that these data are difficult to compare directly. “Without a third-party independent organization that evaluates these vaccines under the same experimental conditions, it is difficult to really draw conclusions.” Jinxia said.
T cell responses are equally important, but only the data on T cells of the Oxford University vaccine impressed scientists. Xu Jianqing said that there are 856 and 424 T cells in one million cells of the Oxford vaccine at 14 days and 56 days, respectively. For comparison, at 28 days, there are about 100 T cells among the million cells of Cansino vaccine, that is, Even the data at 56 days of vaccination with Oxford vaccine is 4 times higher than that of Cansino.
On August 13, the inactivated vaccine of Sinopharm Wuhan Institute published specific test results in the Journal of the American Medical Association. In phase I clinical, 14 days after three vaccination, the average titers of neutralizing antibodies in the low, medium, and high dose groups were 316, 206, and 297, respectively; in phase II clinical trials, the average titers of neutralizing antibodies were 316, 206, and 297 respectively; 14 days after the dose of the vaccine, the neutralizing antibody titers were 121 and 247, respectively. The incidence of adverse reactions of this vaccine is not statistically different between the vaccine group and the placebo group, which is lower than the currently published data of other vaccine clinical trials.
But Xu Jianqing said, thisClass vaccines use the entire inactivated virus to stimulate the human immune system, so the activated antibody type is very broad, including a large number of non-neutralizing antibodies. If the patient is re-infected, the risk of symptoms will increase.(ie ADE phenomenon) cannot be ruled out at present, so the follow-up safety remains to be tested in large-scale clinical trials, especially when the vaccinators are exposed to the virus again.
The recombinant protein vaccine of the American biotechnology company Novavax also published the results of phase I/II clinical trials in the New England Journal of Medicine on September 2, and the neutralizing antibody titers induced by it reached the convalescent COVID-19 4 times that of patients.
On August 31, in New Delhi, India, people were tested for the new coronavirus. According to the new crown epidemic data released by Johns Hopkins University in the United States, as of 12:28 on September 7, Beijing time, the cumulative number of confirmed new crown cases in India has exceeded 4.2 million, and the number of new confirmed cases daily is the world’s first. Picture/People’s Vision
The trade-off between efficiency and speed
In the 18th century, the British doctor Edward Jenner used vaccinia to prevent smallpox and was called the “father of vaccines.” A century later, scientists realized that people can be exposed to inactivated viruses to teach the immune system to deal with the virus. Since the 1980s, vaccine giants have generally adopted recombinant subunit protein vaccines. Nucleic acid vaccines are the third-generation vaccine technology developed in the past 30 years. These technologies have a common purpose, that is, how to “deceive” human immunity. System to remember what the pathogen looks like.
To achieve this goal, vaccines can be prepared from weakened viruses, inactivated viruses, partial viral proteins, viral proteins implanted on harmless viruses, or even just mRNA encoding the viral protein code. The vaccination is actually similar to the situation where there is no health hazard.The company’s “S-trimer” protein vaccine and the molecular clamp vaccine of the University of Queensland in Australia.
Jin Xia believes that if the vaccines that I think are good now, in another six months or a year, when the Phase III data comes out, maybe we will see different results. Betting all “bao” to run fastest The vaccine above is risky.
Peter Hotz, a vaccine scientist at Baylor University School of Medicine in Houston, USA, said that the first batch of vaccines may not be the best. They may be partially protective, and over time they will be replaced by better vaccines. “Maybe you can call it a race, but it’s more like a marathon.“
(At the request of the interviewee, Qin Yuan is a pseudonym in the text)
This article is from WeChat official account:China News Weekly (ID: chinanewsweekly) author: Peng Danni, editor: Xiao Ran