Immunisation

How vaccines were made historically Live attenuated – vaccinia, BCG, polio (Sabin) Killed – Rabies (Pasteur), Adjuvanted- alum, Sub-units- Hepatitis B surface protein Conjugated vaccines, Hib, covalently linked to tetanus toxoid, Men B omp Pneumococcus CHO linked to CRM197 (diphtheria t) Men C linked to tetanus Future DNA vaccines- work in mice Vectored in vaccinia Prime-boost Polyvalent- 6 in 1, 23 valent PneumoVax H1N1 influenza A vaccine – AS03 & narcolepsy Individualised APC primed against cancers

Ebola vaccine How to make one             - Whole-cell killed             - Live attenuated             - Sub-unit                         *Conserved sequences : Glycoprotein                         * Immunogenic (works in guinea pigs)                         * Adjuvants - antibodies or T cells             - DNA plasmid             - Vectored - Chimpanzee adenovirus       2. Candidates             - Mice, guinea pig, hamster, non-human primate       3. Pre-clinical trials/evaluation             - Stability - temperature, time             - Purity, toxins, contaminants, LPS,             - Mice immunogenicity                      * Antibody levels                      * Neutralising antibodies                      * T cell responses             - Toxicity and path – in 2 species mice, rabbits • Distribution             - Efficacy in animal models, incl. primates       4. Clinical trials             - There are 2 phases                      * Phase I - immunogenicity in human, tolerability                      * Phase II - efficacy, likely no trials in humans             - Deployment based on safety and immunogenicity in humans and efficacy in animal models       5. Licensure       6. Marketing and distribution