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ANTIBODY. ANTIGEN FROM VACCINE. PLASMA CELL. MACROPHAGE. MEMORY B CELL. STIMULATORY MOLECULE SECRETIONS. ANTIGEN PIECE. MHC II. B CELL. TCR. Step3 T cells regulates B & CTL activation . MEMORY CTL. CYTOTOXIC LYMPHOCYTE (CTL). HELPER T CELL. MEMORY HELPER T CELLS.
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ANTIBODY ANTIGEN FROM VACCINE PLASMA CELL MACROPHAGE MEMORY B CELL STIMULATORY MOLECULE SECRETIONS ANTIGEN PIECE MHC II B CELL TCR Step3 T cells regulates B & CTL activation MEMORY CTL CYTOTOXIC LYMPHOCYTE (CTL) HELPER T CELL MEMORY HELPER T CELLS HOW VACCINE PROVIDES PROTECTION Step1 Macrophage takes in antigen by phagocytosis Step4 Activated B cells make & release antibodies able to neutralize the antigen Step2 Macrophages display pieces of the antigen to helper T cells VACCINE-INDUCED RESPONSES
MEMORY CYTOTOXIC LYMPHOCYTE (CTL) NEUTRALIZING ANTIBODY MACROPHAGE ARRIVING VIRUS MHC I VIRUS ANTIGEN PIECES PLASMA CELL TCR MEMORY B CELL MHC II TCR CTL EFFECTOR MEMORY HELPER T CELL TCR MHC I & Peptide HELPER T REGULATORY CELL INFECTED CELL HOW VACCINE PROVIDES PROTECTION Step1 Macrophage display virus antigen pieces to memory CTL & helper T cell NEUTRALIZAITON Step4 Antibodies quickly neutralize the invader Step3 Memory helper T cells swiftly stimulate antibody secretion KILL WHEN A DISEASE AGENT APPEARS Step2 CTL attack infected cells and kill them
SARS vaccine development strategies Live-virus Expression Vector Multi-epitope directed Attenuated Virus Inactivated Virus Subunit SCoV 1 SCoV Translated SCoV protein sequence Heat/ Chemical treatment Tempe- rature treatment SCoV gene 9762 rAdenovirus SCoV gene SCoV protein/ glycoprotein Epitope-rich frag- ment selection Attenuated SCoV Inactivated SCoV SCoV protein/ glycoprotein Vaccine cocktail formulation Targeting NAbs induction by Speed: Slow Safety:Questionable Efficacy:Questiona- ble Targeting NAbs & CMI induction Speed:Slow Safety:least Efficacy:Question- able Targeting Nab induction Speed:Slow Safety:yes Efficacy:Partial Targeting NAbs & CMI induction Speed:fast Safety:questionable Efficacy:questiona- ble Targeting NAbs & CMI induction Speed:fast Safety:safest Efficacy:most expected
Development of modern day vaccines • PeriodVaccine • AttenuatedKilled Toxoid Subunit Multi-epitopes • directed • 18th century Smallpox (1798) • 19th century Rabies (1895) Thyphoid (1896) Diphtheria (1888) • Cholera (1896) • Plague (1897) • Early Tuberculosis (1919) Pertussis (1926) Diphtheria (1923) • 20th century Yellow fever (1935) Influenza (1936) Tetanus (1927) • Late Polio Polio Hepatitis B • 20th century Measles Rabies Pneumonia • Mumps Miningitis • Rubella • 21th century FMD (UBI Asia) • SARS ? (UBI Asia)
EpiMatrix Conservatrix Immuno-informatics Binding assays T cell assays Peptide construct design In vitro validation Formulation Murine (transgenic) studies VaccineCandidate to UBIA’s SARS Vaccine from Genomics Report of disease Nov., 02, China SARS Genomes Global disease outbreak Feb/Mar., 03 Potential epitopes Validated epitopes SARS-causing Coronavirus (SCoV) identified April, 03 Prototype Vaccine Pre-clinical Testing SCoV genome revealed April, 03