Coronavirus: is China ready for the mRNA vaccine revolution?

Zhuang Pinghui
·6-min read

When the quest for a coronavirus vaccine began, China invested big in what it saw as the safest bet – inactivated vaccines.

State-owned Sinopharm and private company Sinovac worked with government-affiliated labs to work around the clock to design inactivated viruses while construction started on biosecure facilities to meet anticipated demand.

But then came the results from developers of an alternative technology called mRNA.

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The stellar efficacy data from clinical trials by mRNA vaccine pioneers Pfizer-BioNTech and Moderna sent shock waves through the industry, prompting a reassessment of the approach.

A top Chinese health official has since urged companies to look again at the new technology while other domestic players are already making the pivot to embrace what they say is a new vaccine era.

What are the coronavirus mRNA vaccines and how do they work?

In November, soon after Pfizer-BioNTech and Moderna announced an interim efficacy rate of more than 90 per cent for their candidates, the head of the Chinese Centre for Disease Control and Prevention told the country’s vaccine executives that mRNA technology could revolutionise the industry and they should be ready.

Addressing the 4,000 people at the China Biological Products Annual Conference in Zhuhai in southern China, George Gao Fu said it was highly likely that mRNA vaccines would have the ultimate power to fight the coronavirus that causes Covid-19.

“The technology is fast, potent and induces longer immunity, from cellular to humoral immunity,” Gao said, referring to anitbody-mediated immunity.

“You are the heavyweights of the industry. I hope you will give thought tonight about whether your company should make a transition and whether you should start to make arrangements to work on mRNA vaccines.”

Until the United States approved the Pfizer-BioNTech vaccine for emergency use last month, the shots used on people were mostly a safely weakened version of the virus, which triggered the human body to make antibodies to fight the disease proper.

More advanced vaccines revolved around injecting part of the pathogen, such as a protein or sugar, to induce an immune response.

The mRNA vaccines take a different approach altogether – delivering instructions to cells to make useful proteins.

These formulas rely human cells decoding genetic material from the virus and making proteins to fight it. The material, synthetic mRNA, is wrapped in an oily bubble coating made of lipid nanoparticles to be delivered into the human body.

Once in the body, the material fuses to cells and the cell’s molecules decode the genome sequence to build spike proteins, which train the human body to launch an immune response. The mRNA from the vaccines degrades in about 72 hours so it will not combine with human DNA.

We can’t rule out risks with Covid-19 mRNA vaccines, top Chinese health official says

The idea of using mRNA has been around for decades, but had got little beyond early stage human trials for cancer treatment or vaccines for the flu, Zika and rabies.

Then Covid-19 happened and developers looked to unlock the power of mRNA.

Xiang Zuoyun, chief strategy officer with Chinese vaccine developer Walvax Biotechnology, said this was the start of something new.

“[mRNA] is excellent technology for developing viral vaccines in the future and it is very likely that, in 20 or 30 years, all vaccines will use it. The trend is quite obvious,” Xiang said. “I feel we are witnessing the beginning of a new vaccine era.”

Xiang said biological companies should either acquire or foster the technical ability to seize the business opportunities presented by mRNA technology.

One of the big advantages of synthetic mRNA is that it is much easier and quicker to produce in the lab than it is to inactivate or attenuate a virus. Moderna took only two months to design an mRNA vaccine and launch trials after Chinese scientists released the genome sequence of the coronavirus. And, in theory, mRNA can be directed to produce any protein, opening the door to make all kinds of vaccines for infectious diseases or even cancer.

China has a handful of biotech start-ups specialising in mRNA vaccines and drugs, most of which were founded by scientists who gained their expertise overseas.

One start-up is Stemirna Therapeutics, which has been given the green light for Covid-19 vaccine trials.

Two other mRNA candidates jointly designed by Jiaotong and Fudan universities in Shanghai are in preclinical studies.

Walvax is working on its ARCoVax vaccine with the Academy of Military Science and Suzhou Abogen Biosciences. Its candidate entered a phase 1B clinical trial in October and construction started on a factory for it in Yuxi, Yunnan province, last month. The goal is to be in production within eight months with an initial capacity of 120 million doses.

Walvax has tried to shift more of its resources to mRNA vaccines by selling off some stakes in a company in the process of registering its HPV vaccine but this has been blocked by shareholders keen to reap the rewards of the earlier investment.

Other companies are also trying to forge ahead. Last month Chongqing Zhifei Biological Products bought 10 per cent of Shenzhen Shenxin Biotechnology, one of China’s few start-ups developing mRNA vaccines for rare diseases, to increase its core competitiveness.

Zhang Linqi, professor of medicine at Tsinghua University in Beijing, said mRNA was pushed to the forefront for the first time when clinical trials proved it to be safe and effective.

“It has the advantage of being safe, quick to respond and precise in targeting the pathogen,” Zhang said. “If there is a future disease X, the mRNA technology will have a big advantage on the front line in fighting it.”

However, mRNA developers still need to find ways to scale up production, reduce side effects and stablise the mRNA molecules, which can fall apart at room temperature and have to be transported under very cold conditions, according to Zhang.

Heavyweights like Moderna and BioNTech have a head start in this area. Moderna established an mRNA-based pipeline for various infectious diseases, cancer, cardiovascular diseases and rare genetic diseases before the Covid-19 pandemic. It announced earlier this month that the company would start evaluating three candidates for seasonal flu vaccines and two candidates for HIV vaccines, and another as a vaccine against the Nipah virus. BioNTech also has a research pipeline of about 21 cancer drugs.

Coronavirus: China breaks ground on mRNA vaccine plant

Peng Yucai, founder of Zhuhai Lifanda Biotechnology, a biotech start-up specialising in mRNA vaccines and drugs, said good data from large trials of mRNA vaccines in other countries would have a positive influence on drug regulators in China, raising confidence in the new technology and increasing the prospects for such vaccines to be approved in the future.

But the industry needs the government’s help to overcome a possible production bottleneck.

“It’s a burgeoning industry, from the supply of raw materials to the supply of production equipment and it’s the case not only in China but also for the whole world,” Peng said. “The production chain will improve if the government is keen to develop the industry. It’s achievable.”

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