疫苗生产：工艺开发和专业知识

A virus-like particle is a biological nanoparticle consisting of the protective protein shell of a virus without its genome. Mimicking the overall structure of virus particles but lacking infectious genetic material, they represent an appealing model for vaccine development. VLPs can be produced by methods such as mammalian cell culture, insect cell culture, and bacterial and yeast-based systems. While these systems can result in good production yields, purification requires particular attention. The challenge is to develop a scalable upstream process, together with clarification steps and effective purification, while ensuring product quality and reproducibility.

Viral vectors are a promising platform for vaccine development, inducing cell-mediated immunity against complex diseases such as Ebola, RSV, COVID-19, and other emerging threats. They also offer quick-response potential to repurpose a single virus production template for multiple diseases. However, viral vector processes can pose challenges: improving yield to meet patient demand, maintaining biosafety testing standards for product characterization, potency and safety, as well as streamlining time-consuming production to enhance commercial readiness and accelerate therapy to-market. Manufacturers that overcome these challenges can capitalize on viral vector platform opportunities, while improving the response to global health challenges. 

Plasmid DNA (pDNA) is an important component of viral vector or vaccines therapies. pDNA is also used as the starting material for mRNA vaccines.

These circular DNA molecules can be used as therapeutic transgene, to code for the viral capsid or as the vaccine itself. DNA vaccines have been approved for use in animals and have been developed against the SARS-CoV-2 virus.

mRNA vaccines are rapidly developing vaccine type and have clearly demonstrated that they are opening a new era in vaccinology. Nucleic acids are based either on DNA formed from a fermentation process and, on messenger RNA (mRNA), which are synthesized in in vitro systems. They induce or promote an immune response against a large number of potential pathogens. These RNA vaccines are growing in popularity because of their quick turnaround time and cost-effective production of large quantities in the event of an outbreak or pandemic. They are also resilient and offer long shelf life under a variety of storage conditions.

Conjugated polysaccharide (CPS) vaccines are used globally, particularly in children and the developing world. They offer lifesaving protection against a variety of bacterial infections, including pneumonia, Haemophilus influenzae type b (Hib), and meningitis. Because polysaccharide antigens are not very immunogenic in their native state, chemical conjugation with an immunogenic carrier protein is a critical step. CPS vaccine production requires a complex, multi-step downstream purification process that can pose severe challenges for manufacturers under pressure to maximize yield and reduce costs. To keep CPS vaccines affordable for developing countries, state-of-the-art technologies and process design are essential for fast, cost-effective production that also meets specifications.

Toxoid and whole bacteria vaccines induce immunity in a similar manner as CPS vaccines, which also utilize inactivated toxoids or bacteria via chemical conjugation. While these platforms are generally regarded as safe, there are process-related challenges with endotoxin removal and, as with any process, the goal of optimizing recovery and yield. Such challenges must be overcome during process development and implementation in order to assure high-quality product.