New crown vaccine: Taiwan’s first “high-end” vaccine, a few questions you might want to know-BBC News

Before the new crown pandemic, the “High-end Vaccine Biologics Co., Ltd.” established in Taiwan in 2012 was mainly engaged in the development and production of enterovirus and influenza vaccines.

The company website stated that the high-end new crown vaccine production technology was signed with the National Institutes of Health (NIH) to transfer the genetically recombined S-2P spike protein technology to Taiwan. This technology uses genetic recombination technology to produce the spinous protein on the surface of the virus, which is then made into a vaccine and injected into the human body, allowing the latter to produce an immune response to resist the new coronavirus.

Li Bingying, a physician at National Taiwan University Hospital and honorary chairman of the Taiwan Vaccine Promotion Association, said in an interview with a radio program that the high-end new crown vaccine is provided by the National Institutes of Health. He said that the high-end new crown vaccine is completed by himself from research and development to finished products.

The high-end is the world‘s first new crown vaccine to replace the third phase experiment with “immune bridging” technology and pass the local emergency authorization (EUA). Therefore, it has also aroused fierce debate in Taiwanese society.

First of all, the high-end announced the experimental results on June 10 this year to “unblind” and passed.

According to the information provided by the company’s website, about 4,000 people participated in the high-end Phase II clinical trial, and the oldest subjects were 89 years old. Vaccine-related serious adverse reactions occurred”; second, “immunogenesis regardless of age is in line with expectations.” The data “unblinded” was successful, so the high-end immediately applied to the Taiwan government for EUA.

On July 18 this year, Taiwan’s Food and Drug Administration, Wu Xiumei, announced at a regular press conference at the Taiwan Command Center (CDC) that the results of the expert review meeting passed the EUA application for high-end vaccines and approved “project manufacturing.”

Wu Xiumei said that this result is due to the fact that the “neutralizing antibody data” of high-end vaccines has proven not inferior to AstraZeneca (AstraZeneca, AZ vaccine), and the safety data shows that there are no major safety concerns.

In addition, the Taiwan Food and Drug Administration requires that pharmacies must provide monthly safety monitoring reports during the project approval and manufacturing period, and submit reports on the effectiveness of vaccine protection at home and abroad within one year after approval.

However, Huang Limin, the director of the Children’s Hospital of National Taiwan University Hospital, once told the Taiwan Media Health Magazine, “The human test is currently only carried out to the second phase, which can only prove that the safety is no problem, but the third phase of the human test has not been carried out. Knowing that the protection effectiveness can only be estimated from the titers of neutralizing antibodies.”

Taiwan’s opposition Kuomintang chairman Jiang Qichen, after passing the EUA in July this year, went to the court to sue Chen Shizhong, the minister of Taiwan’s Ministry of Health and Welfare, for “profitability”. He believes that there is no way to know if high-end vaccines are clinically less infected and reduce the proportion of severe illnesses than other mainstream vaccines without phase III clinical trial data. Also because of the lack of phase three verification, whether high-end vaccines can effectively combat the disease. A new variant of the virus that is raging internationally now?”

Former Taipei Mayor Hao Longbin held a press conference on August 2 to submit a petition to the Taipei Higher Administrative Court to apply for the suspension of the EUA for high-end vaccines. He said that “immune bridging” is not a technology recognized by the US FDA or the European Union’s drug administration. Report”

“Immune bridging” technology refers to comparing the “neutralizing antibody amount” in the laboratory to replace the results of the third phase experiment.

Chen Xiuxi, a professor at the National Taiwan University Public Health Institute, gave an example to the Taiwanese media health magazine, “If you want to apply for a research institute, you must be eligible: one is to get a degree after a formal graduation, and the other is an equivalent degree. .”

At present, the U.S. Food and Drug Administration (FDA) has not yet accepted vaccines that have been tested for immune bridging to apply for the U.S. EUA.

The third phase of the trial is-barRuguai

According to the press release of the high-end company, the high-end obtained the approval of the third phase of clinical trials in Paraguay on July 20 this year, and began the third phase of human clinical trials with about 1,000 people.

The high-end Phase III trial still adopts the immune bridge design and the AZ vaccine for comparative trials. It is expected to complete all the subject trials in the third quarter of this year, and obtain interim analysis data in the fourth quarter of this year.

Paraguay has a population of approximately 7 million, and the number of confirmed cases of the new crown has so far exceeded 450,000.

Taiwan’s Minister of Health and Welfare Chen Shizhong also revealed on the 16th that Taiwan’s second self-made new crown vaccine “Lianya” failed to pass Taiwan’s “emergency use authorization” review after review, and that Taiwan’s trial report will be resubmitted and the third phase of clinical trials will be carried out simultaneously. , And then continue to apply for listing.

According to the Taiwan Central News Agency, as of August 16, 9.8 million people in Taiwan have received at least one dose of the new crown pneumonia vaccine, and the population coverage rate is about 38.73%. However, only 649,000 people have been given 2 doses, and the population coverage rate is about 2.76%.

“Geometric mean titer of neutralizing antibodies” refers to the antibodies that actually reduce the virus infection rate among the various antibodies produced after the vaccine is injected into the human body.

According to data released by the Taiwan Food and Drug Administration, after comparing the high-end vaccine group with the AZ vaccine group prototype strain, the lower limit of the 95% confidence interval of the geometric mean titer ratio of the high-end neutralizing antibody is 3.4 times, which is 0.67 times greater than the standard requirement. Therefore, through high-end EUA.

However, Chen Zhepei, an academician of the Central Research Institute of Taiwan, told the Taiwan media that the high-end research data through EUA has “no scientific value at all, because the antibody titer is not equal to the actual protective power, and the titer data is very high. It does not mean that it has reliable protection.”

Taiwanese vaccine research expert and Dr. He Meixiang from the Institute of Biomedicine of the Central Academy of Medicine said that the use of neutralizing antibodies as a protective alternative indicator has a legal and scientific background. She explained on Facebook that this method is used in the annual inspection of Taiwanese influenza vaccine regulations when replacing antigens. “The prerequisite behind it is that the experimental methods for quantifying antibodies have been standardized and all use internationally unified standard reagents. Therefore, The antibody levels of each vaccine are comparable to each other.”

Doctor of Epidemiology at Harvard University, Professor Li Jianzhang of National Taiwan University School of Medicine, analyzed in the “Future City” column of Taiwanese media Common Wealth Magazine. The medical community generally believes that protein vaccines (such as high-end) can stimulate antibody production, but the effect of cellular immune stimulation is not good. The new generation of nucleic acid vaccines, including AZ and Moderna vaccines, are vaccines designed for cellular immune stimulation, which can stimulate strong cellular immunity.

Professor Xinru Shi, director of the Center for Emerging Virus Infection Research of Chang Gung University, told Taiwanese media HeHo (Health & Hope): “The high-end neutralizing antibody has a titer of 662, which is just a value. There is no way to directly compare it with AZ and Modena. Or the comparison of neutralizing antibody titers made by Pfizer in foreign laboratories.”

Li Jianzhang said that although the high-end Phase II and results have confirmed that the vaccine produces more antibodies in the human body than the AZ vaccine, this is because the high-end protein vaccine has added adjuvants (ie, immunostimulants), so it can be used in humans. The body produces more antibodies than the AZ vaccine. “This is a phenomenon that can be completely expected in immunology. If you compare the protective power of the two, there is a feeling of’Zhang Fei than Yue Fei’. After all, the principles of the two vaccines are different.”

At present, the Taiwanese government only allows Taiwan residents over 20 years old to administer high-end vaccines.

Li Jianzhang believes that if you are worried that the elderly will not be able to withstand a strong immune response (side effects) vaccinated with AZ or Modena vaccine, you can choose to consider high-end. In addition, he also said that if young people who cannot be vaccinated in the short term need to go abroad intensively under the situation of vaccine shortage, the service industry people who intensively contact the population may also consider high-end vaccination first. The choice of nucleic acid vaccine.”