The cumulative number of confirmed cases of COVID-19 has exceeded 11.30 million worldwide by July 5. The vaccine development has been in full swing in each country since the occurrence of the virus.In the 133 COVID-19 vaccines in development worldwide, nearly 20 have entered the clinical stage. Wherein, the top three countries in terms of the number of vaccines in development are the U.S. (42), China (19), and Canada (11).

Inactivated COVID-19 vaccines featured in China

To date, 5 Chinese-produced COVID-19 vaccines have entered the clinical stage in China, including 1 adenovirus vector vaccine and 4 inactivated virus vaccines, with 3 vaccines in development having been completed the phase II clinical trial.

As China’s national teams for Chinese-produced vaccine development, Wuhan Institute of Biological Products and Beijing Biological Products Institute of CNBG have successively unveiled the phase I/II clinical results of two inactivated COVID-19 vaccines in development in June, with accumulatively 2,240 people enrolled in phase I/II clinical studies of these two vaccines in China.

According to the staged results unveiled of phase I/II clinical trial of Wuhan Institute of Biological Products on June 16, after vaccination, the safety of the vaccine was good, with no serious adverse reaction; high-titer antibodies were produced in the vaccination group after vaccination according to different procedures and different doses; after two doses based on the 0-and-28-day procedure, the neutralizing antibody positive conversion rate reached 100%.

According to the staged results unveiled of phase I/II clinical trial of Beijing Biological Products Institute on June 28, after the low dose, medium dose, and high dose based on the 0-and-14-day procedure, 0-and-21-day procedure, and 0-and-28-day procedure, the vaccine showed good safety and immunogenicity in healthy subjects aged 18 to 59, with vaccinated subjects all producing high-titer antibodies. The COVID-19 vaccines developed have been preliminarily suggested to be safe and effective with reference to the previous similar products and in combination with existing human data.

World’s first phase III international clinical trial of inactivated COVID-19 vaccine

The Sinopharm CNBG Commencement Ceremony for the Phase III Clinical Trial of Inactivated COVID-19 Vaccine in the United Arab Emirates was held on June 23 in Beijing, Wuhan, and Abu Dhabi, which is the world’s first phase III international clinical trial of inactivated COVID-19 vaccine, to be followed by the phase III clinical trials of 2 vaccines in development in China.

The main objective of the phase III clinical trial is to comprehensively evaluate the protective effects and safety of the vaccine in a larger population, which is the basis for obtaining the approval for marketing. China is expected to market the world’s first COVID-19 vaccine through inactivated virus vaccines, as seen from the current progress.

mRNA vaccines for COVID-19 preferred by the U.S. NIH

Different from the development route of inactivated virus vaccines featured by China, mRNA vaccines are the preferred COVID-19 vaccine type of the U.S. NIH.

Pfizer and BioNTech, two bio pharmaceuticals companies, announced preliminary positive Phase 1/2 clinical data from the most advanced BNT162b1 in the BNT162 mRNA vaccines for COVID-19 on July 1. According to the data, BNT162b1 had good safety and produced significantly elevated RBD-binding IgG SARS-CoV-2 neutralizing antibodies at day 28 compared to the convalescent serum group.

It is worth mentioning that this study is the first published clinical trial in the U.S. based on the COVID-19 mRNA vaccine technique. BNT162b1 is a lipid-soluble nanoparticle formulation of trimerized RBD mRNA and a nucleoside-modified mRNA vaccine candidate expressing the SARS-CoV-2 receptor-binding domain (RBD). It is estimated that Pfizer will conduct a large, global Phase 2b/3 safety and efficacy trial in late July and recruit 30,000 subjects.

Differences between China and the U.S. in COVID-19 vaccine development route

An inactivated virus vaccine is a vaccine that is physically or chemically treated to cause the virus to lose infectivity and replication capacity but retain the virus’ activity to trigger an immune response in humans. Inactivated vaccines are vaccine products with prototype viruses entirely inactivated, retain almost all the antigens and epitopes of the viruses, and can target the conserved epitopes of viruses to reduce the possibility of virus escape.

Current inactivated virus vaccines in China have advanced R&D technologies, mature production processes, controllable quality standards, and guaranteed production capacity, compared to other types of vaccines. Beijing Biological Products Institute completed China’s first and only high-level biosafety production facility on Apr. 15, which, after being put into use, will achieve annual production of 120 million doses of COVID-19 vaccine.

However, inactivated virus vaccines normally require multiple vaccinations to produce sufficiently protective antibodies, and the rapid mass production of vaccines is a key challenge.

The mRNA vaccines preferred by the U.S. NIH directly inject the coding RNA of virus antigen protein to human bodies for human cells to synthesize the virus antigen protein to produce immune responses.

Self-amplifying mRNA vaccines and the state-of-the-art trans-amplifying mRNA vaccines can amplify and sustainably express viral antigens in the body and activate the innate immune system and do not require multiple vaccinations, which can save a large number of vaccine doses; their manufacturing process can be easily standardized, with the vaccine raw materials chemically synthesizable. However, mRNA vaccine development has big technical difficulties and poses great challenges to safety and effectiveness; RNA is not stable, and vaccines need to be stored at ultra-low temperatures, with strict requirements for the storage environment.

It’s worth noting that from the perspective of meeting international demands for vaccine deployment, saving vaccine doses was the main consideration for the U.S. NIH’s choice of mRNA vaccine development, which has largely decided the differences between the U.S. and China in the preferred route of COVID-19 vaccine development.

About  the Author:    

Xiaoyaowan, a pharmaceutical industry practitioner, a word carrier in the We-media era focusing on changes of the pharma industry.

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