Introduction
What is the progress of domestic new crown mRNA vaccine, I am afraid that many people are concerned about this topic?
On May 31, Qin Chengfeng, a scholar at the Academy of Military Medical Sciences, and others published a preprinted article in medRxiv disclosing clinical data on the new crown mRNA vaccine ARCoV (AWcorna) developed by Watson Biologics/Aibo Biologics as a booster shot.
The vaccine, which was developed by Watson Biologicals, Abbott Biologicals and the Academy of Military Sciences, was published in January of this year in the Lancet-Microbiology journal as the result of a phase I clinical trial.
At a time when Omicron strains are prevalent and new coronaviruses continue to mutate, how effective and safe is the domestic mRNA vaccine ARCoV? Does it compare favorably with foreign-developed neostriatal mRNA vaccines?
Industry insiders point out that although as a booster shot, ARBio's mRNA vaccine is better than the inactivated vaccine, the concentration of neutralizing antibodies produced by the ARCoV vaccine is still lower compared to the mRNA vaccines already marketed abroad.
By Xiaowei Li and Anqi Li
The new crown pandemic has driven the development of mRNA technology. While foreign pharmaceutical companies have entered the mRNA vaccine circuit, China has not given up the chase in this field, and at least 10 companies are now stepping up the development of new crown mRNA vaccines.
Recently, clinical data on Watson Biologics/Abbott Biologics' new crown mRNA vaccine, ARCoV, as a booster shot was published in preprints, with good efficacy and safety as a booster shot after 2 doses of inactivated vaccine, according to the data in the paper.
However, some industry insiders say that this data is not satisfactory because the antibody titers elicited are not high. For more details, please see: Is the data of Abbott's domestic mRNA vaccine really similar to that of foreign vaccines? Is the booster shot result good?
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Overview of clinical trial of Ablixa's mRNA vaccine booster
The trial included 300 subjects, all adults 6 months after 2 doses of inactivated virus vaccine (CoronaVac or BBIBP-CorV) and a 2:1 ratio of AWcorna mRNA vaccine or inactivated CoronaVac vaccine as a booster shot.
The mean age of the subjects was 43 years in the mRNA vaccine group and 40 years in the inactivated vaccine group, and 16 subjects aged 60 years or older were included, as well as 27 subjects with comorbid underlying disease.
02
What are the efficacy and safety data of the Ablixa mRNA vaccine?
Clinical data results show that on the basis of 2 doses of inactivated vaccine, the heterologous booster vaccination (third dose) of ARCoV by Watson Biologics/Aibo Biologics induces higher neutralizing antibodies than homologous vaccination (inactivated) and has a better safety profile, but we do not yet know whether it will be finally approved.
Data on the efficacy and safety of the vaccine are as follows.
1. Comparison of two vaccines against the original strain and the delta mutant
Neutralizing antibodies induced by ARCov heterologous vaccination were 3.8 and 6.5 times higher than those induced by CoronaVac homologous vaccination. Figure a shows that neutralizing antibodies were significantly higher in the sera of both groups of subjects for both vaccines against the original strain of Neocrown, higher at day 14 than at day 28. In the ARCov group, the increase was from 4.4 before the booster vaccination to 242.4 at 28 days of the booster vaccination; in the CoronaVac group, the increase was from 4.5 before the booster vaccination to 64.3 at 28 days of the booster vaccination.
Figure b shows the neutralizing antibodies in the sera of both groups of subjects for both vaccines against the delta mutant strain, which were also significantly higher, again, at day 14 compared to day 28. In the ARCov group, the concentration increased from 4.2 before the booster vaccination to 257.8 at 28 days of the booster vaccination; in the CoronaVac group, it increased from 4.1 before the booster vaccination to 39.8 at 28 days of the booster vaccination.
2. Comparison of two vaccines against Omicron mutant strains
The high immune escape ability of the Omicron strain explains why previously developed antibodies to the new crown are ineffective against it. The results showed that both vaccines produced much lower concentrations of neutralizing antibodies against the Omicron strain compared to the original strain, confirming previous studies that the Omicron strain has a higher immune escape capacity.
However, mRNA is still somewhat more effective than inactivated vaccines, and ARCov booster vaccination induced 4.4 times more neutralizing antibodies than the CoronaVac booster. Since the concentrations of both neutralizing antibodies produced were low, industry sources have pointed out whether it has value as a booster shot in the real world.
In an article, Dr. Yebin Zhou wrote, "Combining these data, although the heterologous enhancement of ARCoV is higher than the homologous enhancement of inactivated vaccines, it is significantly worse than the mRNA vaccines that have been marketed, and even inferior to adenovirus vaccines that have been gradually replaced by mRNA vaccines abroad."
3. Comparison of the two vaccines in the elderly population aged 60 years and older
For the original strain, neutralizing antibodies increased significantly in both groups after booster vaccination, from 4.0 in the ARCov group before booster vaccination to 152.3 at 28 days of booster vaccination, and from 4.5 in the CoronaVac group before booster vaccination to 30.5 at 28 days of booster vaccination, with the ARCov group being 5 times higher than the CoronaVac group. For the Delta strain, neutralizing antibodies were also significantly higher in both groups of elderly subjects after booster vaccination, 187.5 in the ARCov group and 25.9 in the CoronaVac group at 28 days of booster vaccination, 7.2 times higher in the former than in the latter.
4. Comparison of the safety of the two vaccines as booster shots
No serious adverse events or deaths occurred in either group, with the ARCova group causing more adverse events than the CoronaVac group. the major adverse events in the ARCova group were fever and headache, with the highest number of febrile conditions occurring in the 20 μg and 25 μg groups, followed by the 10 μg group, with fever rates exceeding 50%. the higher rates of grade 3 systemic adverse events were in the 15 μg, 20 μ g group and 25 μg group, which was about 30% of the overall. (Note: so-called grade 3 adverse events are serious or clinically significant, but not immediately fatal, requiring hospital intervention or extended hospital stay)
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The road to mRNA vaccine development for Ablixa
In the early stages of the outbreak, Abbott Biologics initiated the development of a new crown vaccine. In September 2020, Abbott Bio indicated that it had been approved to enter Phase I clinical trials.
In June 2020, the ARCoV vaccine jointly developed by Watson Biologicals, Abbott Biologicals and the Military Medical Research Institute of the Academy of Military Sciences received the first clinical approval for an mRNA vaccine in China. This mRNA-LNP vaccine is a liquid formulation encapsulated in a pre-filled syringe that does not need to be thawed or dissolved prior to injection. It can be maintained at 4-25 degrees Celsius for at least one week.
On April 19, 2021, the Phase II clinical trial of the mRNA vaccine ARCoV (ARCoVaX) is nearing completion and ready to enter Phase III clinical trials overseas.
In September 2021, ARCoV Phase III clinical trials were approved by the Mexican and Indonesian drug regulatory authorities, respectively.
On January 24, 2022, the Phase I clinical results of the first domestic new crown mRNA vaccine were released, assessing the initial safety, tolerability and immunogenicity of the vaccine. See "Clinical Phase I Results of China's First New Crown mRNA Vaccine Released, 10 Key Messages Reveal Important Progress" in the Deep Science History article.
However, this result has also led to mixed reviews from the industry, which believes that it is much inferior to the new crown mRNA vaccine that has been marketed abroad.
The ARCoV vaccine developed by Watson Biologicals and Abbott Biologicals is not the only new crown mRNA vaccine in China, as China Biologicals and S Microbiology are both working on vaccine development in this area. Besides that, Fosun Pharma started to introduce mRNA New Crown vaccine in 2020, and the vaccine development in this area was slowed down due to the previous better control of the domestic epidemic.
The drawbacks of this development as well as review and approval strategy became apparent earlier this year when the Omicron strain came to the forefront. Currently, many domestic pharmaceutical companies are invested in the development of mRNA New Crown vaccines, so hopefully we are not too long away from the process of a domestic New Crown mRNA vaccine.
References
1. Is the data of Abbott's domestic mRNA vaccine really similar to that of foreign vaccines? Is the booster shot result good. A small garden of science for biological dogs.
2. Heavyweight! Clinical phase I results of the first domestic new crown mRNA vaccine announced, 10 key information discloses important progress. In-depth Science
3. Watson mRNA vaccine induced 4.4 times more neutralizing antibodies against Omicron than homologous boosters when administered sequentially as a booster shot. Hanson clinical study
