Viral vaccine production (5 MIN READ)

Production of vaccine industrially explained in 5 min. Factors under consideration and storage. Types of vaccine produced all under one presentation.

1. Viral Vaccine Production SOURABH SANTOSH GURAV MTECH BIOPROCESS TECHNOLOGY INSTITUTE OF CHEMICAL TECHNOLOGY

2. IMPORTANT AREAS FOR A VIRAL VACCINE Five important areas for a viral vaccine are - (1) the choice of the cell substrate (2) the choice of the virus construct (3) bioreactor technology (4) purification (5) final product stabilization.

3. Cell Substrates Human diploid cell lines: Medical Research Council-5 (MRC-5) & Wistar Institute-38 (WI-38) Continuous cell lines : Vero and Madin Darby Canine Kidney (MDCK) recombinant “designer” cell lines: PER.C6 and CAP plant-based recombinant protein production (Not commercial)

4. VACCINE TYPE REMARK EXAMPLES Inactivated Vaccine or killed vaccine Pathogens  that have been grown in  culture  and then lose disease producing capacity Hepatitis A, whole cell Pertussis live vaccines Pathogens are still alive but are almost attenuated , that is, weakened Oral Polio Vaccine, Rotavirus, Tuberculosis (BCG) etc Subunit vaccine Contains a fragment of the pathogen and elicits an appropriate immune response • Diphteria , acellular Pertussis, Subunit influenza Virus - like - particle Vaccine Molecules that mimic viruses but are not infectious Human Papilloma Virus (HPV) Viral Vector Vaccine Uses a chemically weakened  virus  to transport pieces of the pathogen DNA , RNA Vaccine Uses a man-made copy of a natural chemical called  messenger RNA  (m RNA) or DNA to produce an immune response

5. Bioreactor Technology Attachment-dependent modalities such as t-flasks, cell factories, and roller bottles At industrial scale – Small spheres (microcarriers) kept in suspension 6000L scale Single-use bioreactors Facilitates multiproduct manufacturing in facilities and reduces change-over times between batches

6. Microcarrier Cell System Hollow fibre Membrane

7. 1.CELL EXPANSION 2.VIRUS PROPOGATION (BIOREACTOR) 3.Removal of cell debris and large particles 4.CONCENTRATION 5.Separation of virus from small molecular compounds 6.Virus inactivation formaldehyde 5.Formulation Sterile filtration, mixing with other strains typical viral vaccine production process

8. Harvesting of the virus by centrifugation and/or filtration Purification via chromatograph Inactivation as needed with chemical additives Final conditioning with tangential flow filtration Size-exclusion chromatography : purification of whole virus Flow-through chromatography :impurities in the feed are adsorbed to the resin Cell Culture Roller Flask System

9. Virus Stabilization addition of complex stabilizers and via lyophilization for live viral vaccines enable distribution need to supply a separate diluent in addition to the dry powder spray drying have been investigated

10.   spray-drying mechanism

11. STORAGE live-virus vaccines : tolerate freezing temperatures and rapidly deteriorate once defrosted inactivated vaccines : require stable temperatures of 2-8⁰C