Vaccine Composition PDF

2.1. General principles and composition of vaccines Prophylactic versus therapeutic vaccines Prophylaxis Treatment – therapeutic vaccination • Chronic infectious disease • Cancer • Autoimmune disease and allergy • Fertility, abuse (smoking), ... Ideal Vaccine Safe, no side effects Single dos...

2.1. General principles and composition of vaccines Prophylactic versus therapeutic vaccines Prophylaxis Treatment – therapeutic vaccination • Chronic infectious disease • Cancer • Autoimmune disease and allergy • Fertility, abuse (smoking), ... Ideal Vaccine Safe, no side effects Single dose Long-lasting immunity (life-long) Protective immunity against - severe disease - mild-moderate disease - infection (no transmission) Vaccine development New vaccines for diseases not previously vaccine-preventable or posing a new medical need Improvement of existing vaccines, e.g. • Redesign vaccine structure • Improve production process • More potent formulation • Increase stability of final product Vaccine design: important decisions to make 1. Choice of antigen/immunogen 2. Overcoming pathogen diversity 3. Defining correlates of protection 4. Delivery of antigen to immune system 5. Route of immunization 6. Antigen dose 7. Number of vaccine doses 8. Using adjuvants Vaccination: active/passive Active immunisation Induces an immune response “in vivo” • Humoral • Cellular Antibodies (IgG, IgA, ..) Th1, Th2, TFH, Th17, CTL, Treg Passive immunisation • Administer antibodies (poly-, monoclonal) • No active vaccine available • Immune compromised subject • Immediate action required Vaccine administration Administration site Administration route Anterolateral thigh (≤ 1 year) Deltoid muscle (> 1 year) Intramuscular (IM) route: standard Subcutaneous (SC) route Intradermal (ID) route: antigen sparing Oral Intranasal Intranasal Oral DNA vaccine delivery system (PowderJect; investigational) Vaccination schedule - Number of doses: 1, 2, 3, 4 dose-schedule - Once in a lifetime versus repeated vaccination - Priming dose(s) versus booster dose(s) - Revaccination versus boosting Composition of vaccines Polling question 1 Which of the following is not a regular constituent (active component, trace element) of an inactivated seasonal influenza vaccine? A. Haemagglutinine B. Gentamycine C. Thiomersal D. Culture material (e.g. egg protein) E. I don’t know Common components of vaccines Active components A form of the pathogen that causes the disease is used as the antigen. It is modified to cause no disease but still induce a protective immune response. Adjuvant Al(OH)3 AlPO4 Adjuvants are added to the vaccine to enhance the body’s immune response to the antigen. (+ Adventitious agents) 11 Ingredients of a vaccine Antigens: Live attenuated, inactivated (killed), subunit (incl. toxins) Residues/trace components: Inactivation residuals: Adjuvants formaldehyde Excipients: Cell culture materials: antibiotics, Diluents: aqua, PBS Stabilisers: sucrose, lactose, HSA, BSA, gelatin bacteria, yeast, cell residues Adventitious agents: BSA, porcine circoviruses, … Preservatives: thimerosal (thiomersal), phenoxyethanol PBS: phosphate buffered saline, HSA: human serum albumin; BSA: bovine serum albumin http://edition.cnn.com/2010/HEALTH/03/22/rotavirus.vaccine/index.html http://edition.cnn.com/2010/HEALTH/03/22/rotavirus.vaccine/index.html Polling question 2 How long does the traditional vaccine manufacturing process take, i.e. how much time from the generation of the antigen to the packing of the vaccine? A. 1-8 weeks B. 2-8 months C. 9-15 months D. 9-22 months E. I don’t know Vaccine manufacturing process Step 1: Generation of the antigen and uniformily mixing them • Viruses: on cell cultures Step 5: Packaging • Bacteria: in biofermentors • Recombinant proteins: yeast, cell cultures, bacteria Step 2: Release and isolation of the antigen Step 3: Purification of the antigen Step 4: Formulation of the vaccine i.e. combining all components Nicotiana tabacum Compliant with GMP standards GMP: Good Manufacturing Practices Production of influenza vaccines takes 7-8 months from surveillance to flu shot Polling question 3 How long does the mRNA vaccine manufacturing process take, from vaccine design to manufacturing to shipment A. ± 7 days B. ± 7 weeks C. ± 7 months D. I don’t know mRNA vaccine technology Advantages - High efficacy (Pfizer BioNTech and Moderna approaches) - More reliable and quicker production, rapidly adaptable, no cell culture or bacterial fermentation needed - Same production set-up can be used for several vaccines Disadvantages - Not stable at higher temperatures (although this has already improved a lot since 2020)