1. HOW VACCINE PROVIDES PROTECTION STIMULATORY MOLECULE SECRETIONS B CELL MACROPHAGE Step1 Macrophage takes in antigen by phagocytosis Step2 Macrophages display pieces of the antigen to helper T cells VACCINE-INDUCED RESPONSES ANTIGEN FROM VACCINE MEMORY HELPER T CELLS Step4 Activated B cells make & release antibodies able to neutralize the antigen ANTIBODY PLASMA CELL MEMORY CTL Step3 T cells regulates B & CTL activation CYTOTOXIC LYMPHOCYTE (CTL) HELPER T CELL ANTIGEN PIECE MHC II TCRMEMORY B CELL

2. HOW VACCINE PROVIDES PROTECTION WHEN A DISEASE AGENT APPEARS MHC I TCR MEMORY CYTOTOXIC LYMPHOCYTE (CTL) TCR CTL EFFECTOR KILL INFECTED CELL MHC I & Peptide Step2 CTL attack infected cells and kill them NEUTRALIZING ANTIBODY PLASMA CELL MEMORY B CELL NEUTRALIZAITON Step4 Antibodies quickly neutralize the invader Step1 Macrophage display virus antigen pieces to memory CTL & helper T cell MACROPHAGE ARRIVING VIRUS Step3 Memory helper T cells swiftly stimulate antibody secretion HELPER T REGULATORY CELL MEMORY HELPER T CELL TCR VIRUS ANTIGEN PIECES MHC II

3. SARS vaccine development strategies Targeting Nab induction Speed: Slow Safety: yes Efficacy: Partial SCoV gene SCoV protein/ glycoprotein Subunit Translated SCoV protein sequence 1 9762 Epitope-rich frag- ment selection Vaccine cocktail formulation Targeting NAbs & CMI induction Speed: fast Safety: safest Efficacy: most expected Multi-epitope directed SCoV Inactivated SCoV Heat/ Chemical treatment Targeting NAbs induction by Speed: Slow Safety: Questionable Efficacy: Questiona- ble Inactivated Virus Attenuated SCoV Tempe- rature treatment SCoV Targeting NAbs & CMI induction Speed: Slow Safety: least Efficacy: Question- able Attenuated Virus rAdenovirus SCoV protein/ glycoprotein Targeting NAbs & CMI induction Speed: fast Safety: questionable Efficacy: questiona- ble Live-virus Expression Vector SCoV gene

4. Development of modern day vaccines Period Vaccine Attenuated Killed Toxoid Subunit Multi-epitopes directed 18 th century Smallpox (1798) 19 th century Rabies (1895) Thyphoid (1896) Diphtheria (1888) Cholera (1896) Plague (1897) Early Tuberculosis (1919) Pertussis (1926) Diphtheria (1923) 20 th century Yellow fever (1935 ) Influenza (1936) Tetanus (1927) Late Polio Polio Hepatitis B 20 th century Measles Rabies Pneumonia Mumps Miningitis Rubella 21 th century FMD (UBI Asia) SARS ? (UBI Asia)

5. Immuno-informatics In vitro validation Vaccine Candidate SARS Genomes Potential epitopes Validated epitopes Prototype Vaccine Pre-clinical Testing Peptide construct design Binding assays T cell assays EpiMatrix Conservatrix Formulation Murine (transgenic) studies Report of disease Nov., 02, China Global disease outbreak Feb/Mar., 03 SARS-causing Coronavirus (SCoV) identified April, 03 SCoV genome revealed April, 03 Genomics from Genomics UBIA’s SARS Vaccine to UBIA’s SARS Vaccine