People's Daily health client reporter Shi Mengzhu
"Looking back at the history of human struggles with infectious diseases, whether it is smallpox or polio, the ultimate elimination of these diseases is the hero or vaccine." On April 22, in an interview with the People's Daily health client "People's Famous Artists", Zhang Yi, chairman of Yisheng Biopharmaceutical Co., Ltd., called for the response to the new crown virus, we must pay attention to the research and development of broad-spectrum new crown vaccines, and the vaccine research and development idea of "responding to changes with no change" should be paid attention to.
Yi Zhang, Chairman of Yisheng Biotech
The research and development of new crown vaccines should "respond to changes with no change"
At the beginning of the outbreak of the new crown epidemic, Zhang Yi, who had focused on vaccine research and development for decades, realized that to solve the problem of virus epidemic, it was necessary to develop a universal vaccine that "responded to changes with no change".
Zhang Yi introduced that the vaccines developed based on the original virus strain can effectively fight the infection of the original virus strain, but the current new crown virus continues to mutate, and variants such as Delta and Omicron are emerging in an endless stream. In order to quickly defeat these mutants, the scientific community and the mutants are engaged in a time contest.
"Although the incidence of severe diseases has decreased after receiving existing vaccines, the most important function of vaccines is still to prevent infection after the virus has invaded the body, rather than to reduce the incidence of severe diseases. The World Health Organization stipulates that the effectiveness rate of the new crown vaccine to prevent infection cannot be less than 50%, which is the gold standard for evaluating the effectiveness of the new crown vaccine. Zhang Yi said that we must pay attention to the research and development of a broad-spectrum new crown vaccine.
"The vaccine developed for the original strain of the virus can effectively fight the infection of the original strain of the virus, but now the virus has mutated many times, so the original strain of vaccine can not fight the infection of the Olmiqueron strain; if the vaccine developed with the Olmicoren strain is used, it may not be able to fight against the new variant strain."
For example, Zhang Yi said that the nine virus strains corresponding to the nine-valent cervical cancer vaccine are all circulating at the same time, so the nine-valent vaccine is useful, if only the one-valent virus strain is prevalent, the eight-valent component of the nine-valent cervical cancer vaccine has no significance. The new crown virus is constantly mutating, and the speed of vaccine research and development will never catch up with the speed of virus mutation, so Zhang Yi believes that it is necessary to use the technical idea of "responding to changes with no change" to develop a new crown vaccine.
To achieve a vaccine that "responds to change with the same", two problems must be solved first
In order to develop a new crown vaccine that "responds to changes with no change", Zhang Yi believes that two problems must be solved: one is the antigen design, and the other is to choose a new adjuvant, both of which are indispensable.
Many years ago, Zhang Yi got inspiration in the research and development of AIDS vaccines, and he found that a big difficulty in the development of AIDS vaccines is that the virus mutates quickly, so it has not been possible to develop an AIDS vaccine. If a stable AIDS antigen can be designed, it is not possible to achieve "unchanged response to change". After many trials, good test results were obtained. When the new crown epidemic occurred, Zhang Yi decisively decided to use this IDEA of AIDS vaccine research and development to develop a new crown vaccine to solve the problem that the vaccine could not effectively protect the body infection after the new crown virus mutation.
The second is how to choose an adjuvant.
Adjuvants, also known as immunomodulators or immune enhancers, are an additive of vaccines, when it is injected into the body before or mixed with antigens, it can enhance the body's immune response to antigens or change the type of immune response. Zhang Yi introduced that the ideal adjuvant can not only produce corresponding antibodies, but also activate non-specific and specific cellular immunity, so that the body is in the best immune state.
Eison uses its Pikazog (PIKA) technology with its own intellectual property rights. The combination of recombinant S protein trimer and picazole can quickly induce a strong and long-lasting immune response, induce the production of high levels of neutralizing antibodies and cellular immunity, and can not only effectively fight against the existing major global epidemic strains (including the original strain, D614G, Alpha, Beta, Gamma, Delta, Lambda and Omicron), but also because of its broad spectrum characteristics, it is also expected to fight against future variants. Studies have shown that the pickup recombinant protein novel coronavirus vaccine, although it has reduced the titer of neutralizing antibodies to Delta and Omilon, is still above the level of protection.
According to Zhang Yi, picard adjuvant was listed as a major national new drug creation project in 2018, filling the gap that there is no new adjuvant in China. Using this adjuvant, Eison has developed a number of therapeutic vaccines and anti-cancer drugs. "With the support of the national major new drug creation project, we have optimized and transformed the picard adjuvant, achieved large-scale production, and applied to a number of therapeutic vaccines and anti-cancer drugs, of which the therapeutic pickup rabies vaccine has twice been supported by the national major new drug creation project and is about to enter phase III clinical trials."
In addition to rapid onset of action, immune persistence is also one of the characteristics of the Picazole vaccine. "Pickup recombinant protein new crown vaccine is a broad-spectrum new crown vaccine independently developed by Yisheng Bio. The animals that were immunized in May 2020 have received 600 days of high-level antibody protection, reaching two years soon, and the antibody titer remains at a high level, and can effectively fight against mutant strains such as Omicron. Zhang Yi introduced.
Vaccines go to the masses, and there is still a way to go
"As a researcher and entrepreneur, seeing the recurrence of the epidemic and the rise of the infected population, I feel the responsibility to quickly promote good products around the world." It is reported that Yisheng Bio has submitted clinical declaration materials for pickup recombinant protein new crown vaccine to the drug regulatory agencies in seven countries, including China, the United Arab Emirates, New Zealand, Singapore, Tunisia, Turkey and Laos. Among them, the United Arab Emirates, New Zealand, Singapore, Tunisia and Turkey have successively approved the vaccine to enter clinical trials.
Zhang Yi introduced that at present, the Phase I clinical trial for basic immunity and enhanced immunization against inactivated new crown vaccine and mRNA new crown vaccine in the United Arab Emirates has been basically completed, and the test results show that the serum neutralizing antibody titer on the 7th day after the inactivated vaccine reinforced injection has reached a peak, and the serum neutralizing antibody titer of the Omilton wild strain on the 28th day has reached 583.5, showing that the pickup recombinant protein new crown vaccine effectively fights against the Omilton mutant strain and produces strong protective power.
"Judging from some of the data obtained so far, the safety of the vaccine is similar to the data obtained from clinical trials of other pickup vaccines, and the adverse events are all mild events and the safety is good." Zhang Yi said that these data support larger Phase II/III clinical studies.
The preclinical study of the pickup recombinant protein new crown vaccine also showed that the vaccine maintains a high level of neutralizing antibody activity on a variety of epidemic strains, including Omiljung, with four characteristics such as broad spectrum, rapidity, high efficiency and immune persistence, and at the same time, compared with other recombinant protein vaccines in the world, the pickup recombinant protein new crown vaccine can obtain a high immune effect at 5 micrograms of low-dose immunity, and is at the international leading level in terms of efficacy and safety.
It is reported that at present, Yisheng Bio has built a new crown vaccine production base with a production capacity of billions of doses in Shenyang, Liaoning Province. It is worth mentioning that after strict review and inspection by the regulatory authorities, at the end of March, Yisheng Bio's new crown vaccine production base officially obtained the "Drug Production License" issued by the Liaoning Provincial Food and Drug Administration, which means that Yisheng Bio has the conditions for large-scale production of new crown vaccines. "The localization of the equipment and raw materials used in vaccine production is high, and it is less affected by international supply constraints, which has realized the localization of the whole chain of new crown vaccines and solved the problem of dependence on imports." Zhang Yi stressed.
"We have been working hard for the vaccine to go to the public as soon as possible and serve the public, at present, the subtypes of the Omiljun strain continue to appear, and the interval between new variants to replace the old variants is getting shorter and shorter", for how to better deal with the new coronavirus variant strain, Zhang Yi suggested: "Carry out solidarity trials of the unsolicited, clinical and marketed COVID-19 vaccines that have completed efficacy, safety, and quality controllability, and select high-quality COVID-19 vaccines, and provide support from various policies to accelerate the listing of new high-quality vaccines." ”
Resources:
Liu Y, Dai L, Feng X, et al. Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA. Mol Biomed 2, 29 (2021). https://doi.org/10.1186/s43556-021-00054-z
Yuan Liu, Nan Zhang, Bin Wang, Yi Zhang. Broad and Long-lasting Immune Response against SARS-CoV-2 Omicron and Other Variants by PIKA-Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine (YS-SC2-010). BioRxiv.
