In the third year of humanity’s struggle against COVID-19, the study of new vaccine technologies has become a research field that has attracted much attention. Where are global vaccine technologies going? Do we know enough about our vaccines?

Prof. Ren Sun, chair professor at Westlake University and senior advisor to our university president, was invited to share with us his views on these questions and discuss the latest technology in vaccine research and development, production and use.

In 1986, Sun went to study in the United States after graduating from Fudan University. He studied at Yale University under George Miller, who was taught by the "father of modern vaccines" and Nobel Prize winner John F. Enders. Sun, served as a distinguished professor at the University of California, Los Angeles (UCLA), a chair professor at the University of Hong Kong, and a scientific advisory committee member of the National Cancer Institute. In 2022, Sun joined Westlake University full-time.

Sprayable and Stickable Vaccines

What would the ideal vaccine look like? Is a sprayable and stickable vaccine achievable? Prof. Weike Pei from Westlake University’s School of Life Sciences and the audience asked these questions of. Sun.

As an outstanding scholar who has been engaged in virology and immunology research for a long time, Sun is also known as a "new vaccine designer". Since the outbreak of COVID-19, vaccination rates have been a concern of many. Most of the current vaccines need to be injected by doctors and nurses at a hospital or similar location. During an outbreak, it is risky to go to public places for vaccination, and compliance is also a challenge.

Sun believes that an ideal vaccine should be more convenient. If there is a new outbreak, the vaccine should be able to be couriered to people's homes after production, allowing everyone to complete the vaccination independently. Through this method, vaccination rates would be greatly improved.

One example of a self-deliverable vaccine would be one that can be directly sprayed in the nose. There is already a nasal spray flu vaccine, and Sun’s team is also working on a dual vaccine for influenza and COVID-19 which uses the influenza virus as a carrier to establish immunity through the nasal spray. There is another possible way, using nanotechnology to put the vaccine on tiny needles, sticking tens of thousands of needles to the skin, and then taking it off after a few minutes.

"Such a delivery method will fundamentally change the bottleneck of vaccination,” Sun said. “It can deliver the vaccine to a huge population at a high speed, and it can be delivered to a large number of people within a few days. I think we should have platforms for this technology at Westlake University. I look forward to working with colleagues from Westlake University in this area.”

Plant-based Vaccines

In February 2022, Canada approved a plant-based COVID-19 vaccine. This was the world's first approved plant-based human vaccine, which has gained widespread attention.

Using plants to produce protein in order to improve the speed of response in the event of a major epidemic, saving valuable emergency time, is also one of the directions explored by Sun and his collaborators. In addition to updates in the vaccine delivery, speeding up production is also important. "Most of the production of vaccines requires very expensive cell reactors, which costs tens of millions, and the production speed is not the fastest. So, we want to build a new system to quickly produce vaccines."

This system is a plant factory. Growing plants can quickly produce protein, and plants only need greenhouse conditions such as light, water, and salt, and soilless cultivation can produce protein with improved quality stability and greatly reduced costs. According to Sun, the process of protein production in plant factories is to first cultivate plants, then add the protein you want to synthesize into Agrobacterium, and then sprinkle Agrobacterium on the leaves of plants and deliver them to plant cells, letting plant cells produce recombinant proteins.

This process only takes one week to get kilograms of protein, enough for the population of a province to be vaccinated. The Center for Infectious Disease Research, where Sun is located, has worked with other teams to build this system. In the future, if a new outbreak emerges, emergency medical centers can quickly respond and produce vaccines.

Precise Design

In addition to these interesting new ideas in vaccine production and delivery, Sun also discussed breakthroughs in vaccine design approaches. Over the past 10 years, Sun’s team has been studying the use of high-resolution means to identify the functions of the virus genome, and then through a deep understanding of the virus, to modify the virus and improve its immunogenicity.

Sun’s team was able to analyze the functional map of the whole virus genome at single nucleotide precision for the first time, and based on this map, they were able to accurately design a virus vaccine at the single amino acid level, another first. The effective influenza vaccine candidate strains provide new ideas for the development of broad-spectrum vaccines.

Also a first, Sun's team decoded the structure of an asymmetric RNA virus genome at atomic resolution, providing another avenue for developing novel vaccine designs.

Currently humanity is fighting multiple COVID-19 variants. Sun hopes to lead his team to adopt this new design idea to develop a vaccine with an effective and broad-spectrum immune response.

Ten years ago, Sun began his exploration into new vaccine technology. At the time, his research had not received much attention. He believed that this would be a long-term effort, and he did not expect that this research would have such important practical significance today. Best of all, his broad-spectrum vaccine development ideas can be applied to other viruses too.