Ten year vaccine technology revolution: how to rewrite the global epidemic prevention pattern from COVID-19 mRNA to cell culture black technology?
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- Apr 23,2025
Summary
This article provides a comprehensive summary of the development of vaccine technology over the past decade, including the emergence of new vaccine platforms, the approval status of various vaccines, advances in production technology, and improvements in analytical and characterization capabilities.
1、 Progress and approval status of vaccine research and development
1. New platform vaccine approved
The development of vaccines containing DNA and RNA (viral vector and mRNA LNP vaccines) has been rapid. Since 2012, ten new viral vector vaccines (such as vaccines against Japanese encephalitis, dengue fever, Ebola, SARS-CoV-2, etc.) and two mRNA LNP vaccines have been approved.
Some viral vector vaccines adopt special strategies, such as heterologous strategy (GamEvac Combi), using different vectors (such as VSV/Ad5) to carry antigens.
2. New developments in traditional vaccines
In 2012, Flucelvax became the first seasonal influenza vaccine produced using cell culture technology introduced in the United States, using suspended MDCK cell culture. It was approved in Europe in 2007.
In 2017, FDA approved a variety of vaccines, such as the herpes zoster vaccine Shingerix (recombinant glycoprotein antigen, produced in CHO cells, containing specific adjuvant), hepatitis B vaccine Heplisav - B (containing new adjuvant and recombinant protein subunit antigen).
In 2019, the FDA approved the smallpox and monkeypox vaccine JYNNEOS (a live vaccine produced from MVA-BN strain, grown in specific cells and processed through multiple steps). In 2022, its administration method was extended due to emergency use authorization.
In 2020, WHO approved various polio vaccine related advances, such as nOPV2 (an improved strain prepared using Vero cells with genetic modifications to enhance stability) and sIPV (Vero cell production based on microcarriers with multiple improvements to reduce risk).
3. COVID-19 vaccine achievements
After the outbreak of COVID-19 in early 2020, numerous candidate vaccines entered clinical trials, and the first batch obtained EUA in December of the same year. By March 2023, over 13 billion doses had been administered.
The main vaccine modes include whole virus inactivation (such as Sinovac CoronaVac, BBIBP CorV, etc.), mRNA LNP (such as Pfizer BioNTech Comirnaty, Moderna Spikevax), and adenovirus vectors (such as AstraZeneca Vaxzevria, CanSino Ad5 nCoV, etc.). Different vaccines have their own characteristics in terms of dosage, adjuncts, cells, stability, etc.
2、 Progress in vaccine production technology
1. The selection of cell lines for vaccine production using adherent cell lines in cell culture varies over time, and due to safety considerations, the use of continuous cell lines has increased from restricted to increased.
For example, the rVSV Δ G-ZEBOV-GP Ebola vaccine is produced in Vero cells, and its viral strain has specific modifications.
Innovative development of disposable bioreactors, such as SUB with large surface area per unit volume, and the combination of fixed bed reactors to enhance continuous and automated disposable bioprocessing methods. The polio vaccine embodies a complete process connection from upstream cell culture, downstream processes to inactivation.
suspension culture
Multiple vaccine applications, such as suspension culture of rod-shaped virus expressed insect cells (Sf9), are used for large-scale production of influenza vaccine HA protein.
2. Traditional Applications and New Developments in Microbial Production
The microbial fermentation platform is used to produce a variety of vaccines, for example, the L1 protein of HPV expressed by Saccharomyces cerevisiae is assembled into VLP to produce Gardasil vaccine, the surface antigen of hepatitis B virus can be expressed by Saccharomyces cerevisiae or Pichia pastoris, and the pneumococcal conjugate vaccine is formed by combining the expression components of specific strains.
New cultures have made progress, such as the Dyadic platform based on Thermothelomyces heterohallica fungal cultures, which can rapidly develop stable strains, high yields, easy scalability, and cost-effectiveness.
The COVID-19 candidate vaccine expressed by it is currently undergoing clinical evaluation. MIT's automated platform based on Pichia pastoris can produce a variety of proteins, including vaccine antigens, currently used for the production of rotavirus candidate vaccines.
For protein antigen production, facing the challenge of producing vaccines that expose key epitopes, Escherichia coli fermentation is the main method for producing pDNA templates in mRNA vaccine production.
There has been progress in cell-free synthesis of pDNA, but cost-effectiveness needs to be improved. Additionally, pDNA production has relevant considerations in strain selection and sequence characteristics, and new methods for producing conjugate vaccines have emerged.
Equipment Innovation and Development Trends
The fermentation equipment is transitioning from stainless steel pressure vessels to disposable bioreactors, which have many advantages (such as eliminating cleaning and sterilization steps and improving flexibility), but are limited by process conditions to a maximum scale of about 3000L.
The purification process has established disposable options (from deep filtration to chromatography columns), vaccine manufacturers are striving to establish a disposable system supplier system, and the industry is jointly promoting sustainable recycling and circular economy strategies for disposable components.
