Several Domestic New Crown Mrna Companies Turn To Developing Broad-Spectrum Vaccines, Exploring Against Different Mutant Strains

From the current point of view, many domestic new crown mRNA vaccines are turning to developing broad-spectrum vaccines in. How effective is a broad-spectrum mRNA vaccine in fighting neo-crown virus? What new breakthroughs have been made by domestic mRNA vaccine companies?

In the past two days, Shiyapharm Group (01093.HK) and Kangxino Bio (06185.HK, 688185.SH) have announced that their new crown mRNA vaccines have received clinical trial approvals to enter clinical studies.

Buoyed by the above news, the Hong Kong share prices of both companies jumped more than 5% on the morning of April 4.

Interestingly, both of the aforementioned neo-crown mRNAs under development carry some broad-spectrum properties in an attempt to combat multiple neo-crown mutant strains. The continued mutation of neo-crown viruses is making the existing marketed vaccines less effective in preventing infection and there is an urgent need for a new generation of vaccines to be put into use. At present, many domestic mRNA vaccines are moving towards the development of broad-spectrum vaccines.

How effective are broad-spectrum mRNA vaccines in fighting new coronaviruses? What new breakthroughs have been made by domestic mRNA vaccine companies?

Exploring the development of broad-spectrum mRNA vaccines

In the morning of April 4, Kangxino Biologicals announced that the new coronavirus mRNA vaccine developed by the company had received approval from the State Drug Administration for drug clinical trials, and the results of preclinical studies showed that the vaccine could induce high titers of neutralizing antibodies against a variety of WHO-identified important mutant strains (including the current prevalent strains), which is more broad-spectrum than the existing neo-coronavirus vaccine developed on the basis of the prototype strain.

It is more broad-spectrum than the existing New Crown vaccines based on the prototype strains and provides more effective protection against existing variants.

The night before, another company, Shih Pharmaceutical Group, also announced that its new coronavirus mRNA vaccine ("SYS6006") had been approved by the State Drug Administration to conduct clinical studies in China.

According to the announcement, SYS6006 is an independently developed mRNA vaccine against a novel coronavirus variant. The product is designed with targeted antigenic mutations based on the prevalence of the strain.

Preclinical studies have shown that the product has good immune protection against the current mainstream mutant strains including Omicron and Delta; it provides immune protection through humoral and cellular immunity and can generate memory B cells to provide long-lasting protection. In addition, pre-clinical safety evaluation data also fully demonstrate the safety of the product.

From the above, both of these new crown vaccines are broad-spectrum in nature.

In addition to the two companies mentioned above, on March 31, the first financial reporter also learned from Jia Chen Xihai (Hangzhou) Biotechnology Co., Ltd. that the company and Minhai Biologicals jointly developed the mRNA neo-crown vaccine, and have now completed the validation and evaluation of the immune effect of Omicron vaccine and multivalent vaccine, and the prepared Omicron variant mRNA vaccine can induce high titers of neutralizing antibodies in mice.

The continued mutation of the new coronavirus has weakened the preventive effect of existing vaccines available on the market. Since its first appearance in Tianjin in January this year, the highly infectious variant of Omicron has spread to more than 20 provinces across China. One of the advantages of developing multivalent vaccines is that they can deal with multiple mutations of the virus at the same time and have a broad spectrum.

Recently, Jiang Shibo, director of the Institute of Pathogenic Microbiology at Fudan University, said in an interview with Firstrade that different technological platforms have different strategies for developing broad-spectrum vaccines, for example, the mRNA vaccine technology route can improve the immune response and broad-spectrum by modestly changing the vaccine antigen or adding intramolecular immune adjuvants.

Challenges and breakthroughs

However, the effectiveness of broad-spectrum mRNA vaccines against Omicron mutants and whether they can truly address breakthrough infections of new coronaviruses remains to be validated in clinical studies as well as real-world studies.

Notably, no absolute criteria have been established as to what the relationship is between the level of antibodies, the level of cellular immunity and the preventive efficacy of a neo-crown vaccine, which has made neo-crown vaccine development difficult.

"The path to vaccine development would be much smoother if there were absolute indicators, and precisely because of the lack of relevant standards, the current development of a neo-crown vaccine, which requires large-scale phase III clinical trials, must be judged by effectiveness indicators, which not only greatly increases the difficulty of vaccine development, but also raises the cost of development." Recently, Zhang Lunan, executive director and vice chairman of the board of directors of Aidevision Biologics, told the first financial reporter.

This time, Convivio Bio cautioned in the announcement that the safety and efficacy of the company's novel coronavirus mRNA vaccine is subject to confirmation by clinical studies, and the company cannot guarantee that it will be able to ultimately develop or commercialize a novel coronavirus mRNA vaccine successfully.

Since the emergence of the new coronavirus epidemic in 2020, the new coronavirus mRNA vaccine has been highly regarded by the industry and sought after by capital due to its short development cycle as a new vaccine technology route.

As a type of nucleic acid vaccine, mRNA vaccines are based on the principle of injecting mRNA encoding antigenic proteins directly into human cells, using human cells to produce protein antigens and activate an immune response; the vaccine does not integrate with human DNA and there is no risk of exogenous viral infection. mRNA vaccines work through the following steps: mRNA is encapsulated by various delivery vehicles; injection into the body. The liposomal cytosol encapsulating the mRNA enters the cell; the mRNA is released intracellularly and uses the body's organelles to translate and express the antigenic protein, stimulating an immune response.

For the development of new mRNA vaccines, in addition to the efficacy of the vaccine, the delivery system, production process and storage and transportation of such vaccines need to be explored, with the specific delivery of mRNA into the target cells being a major challenge. The bottleneck in production is the raw material and the scale of production.

It is worth mentioning that some breakthroughs are already being attempted by domestic mRNA vaccine companies.