Live attenuated vaccines are created by weakening a pathogen so that it can no longer cause disease in healthy individuals but still elicits a strong immune response. They are commonly used for diseases like measles, mumps, rubella, and yellow fever. However, they require careful storage and are not recommended for immunocompromised individuals.

Inactivated vaccines are produced by killing the pathogen, rendering it incapable of causing infection while preserving its ability to trigger an immune response. Examples include the polio (IPV) and hepatitis A vaccines. They often require multiple doses or booster shots to maintain immunity but are safe for use even in immunocompromised individuals.

Viral vector vaccines use a harmless virus as a delivery system to introduce genetic material encoding an antigen from the target pathogen. This triggers an immune response without causing disease. They are effective at generating robust immunity and are highly versatile but require careful design to ensure safety and efficacy.

Protein subunit vaccines contain purified components of a pathogen, such as surface proteins, that trigger an immune response without exposing the body to the entire organism. These vaccines are safe, well-tolerated, and suitable for immunocompromised individuals. Examples include the hepatitis B and HPV vaccines. These vaccines may require adjuvants and booster doses to enhance immunity.

Virus-like particle (VLP) vaccines are made from self-assembled viral proteins that mimic the structure of a virus but lack genetic material, making them non-infectious. Examples include the HPV and hepatitis B vaccines. VLP vaccines are safe, highly immunogenic, and increasingly used in modern vaccine development.

mRNA vaccines use synthetic messenger RNA to instruct cells to produce a specific antigen, which triggers an immune response. These vaccines are fast to develop and highly effective, as seen in the COVID-19 vaccines by Pfizer-BioNTech and Moderna. Since they do not use live virus, they are safe and suitable for most individuals.

Virus harvesting occurs after the culturing process is complete and is the first step in downstream processing, aimed at recovering viral particles while removing cell debris and unwanted impurities. This is typically achieved through clarification methods such as centrifugation and filtration, which separate intact viruses from cellular contaminants. Effective virus harvesting ensures high yields and purity, optimizing the subsequent purification process.

Virus purification using centrifugation relies on separating viral particles based on size and density through methods like differential and density gradient centrifugation. Differential centrifugation removes cell debris in successive spins, while density gradients (e.g., sucrose or cesium chloride) isolate viruses at their equilibrium density. These methods effectively concentrate and purify viruses while preserving integrity, but are less scalable compared to filtration or chromatography, making them more suitable for research or small-scale applications.

Virus purification using chromatography separates viral particles from host cell contaminants based on size, charge, and affinity. Unlike protein purification, it requires resins with significantly larger pore sizes to accommodate the greater size and structural complexity of viruses, ensuring efficient flow without clogging. Additionally, shear forces must be carefully controlled to prevent damage to fragile viral particles, particularly enveloped viruses. While protein purification is generally more straightforward and easily scalable due to smaller molecular sizes and standardized methods, virus purification requires careful optimization to achieve high purity and yield while preserving viral integrity, especially in large-scale production.