HOW VACCINE PROVIDES PROTECTIONHOW VACCINE PROVIDES PROTECTIONHOW VACCINE PROVIDES PROTECTIONHOW VACCINE PROVIDES PROTECTION

STIMULATORY MOLECULE

SECRETIONSB 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

TCR

MEMORY B CELL

HOW VACCINE PROVIDES PROTECTIONHOW 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

NEUTRALIZINGANTIBODY

PLASMA CELL

MEMORYB CELL

NEUTRALIZAITON

Step4 Antibodies quickly neutralize the invader

Step1 Macrophage display virus antigen pieces to memory CTL & helper T cell

MACROPHAGEARRIVING VIRUS

Step3 Memory helper T cells swiftly stimulate antibody secretion

HELPER T REGULATORY CELL

MEMORY HELPER T

CELL

TCR

VIRUSANTIGEN PIECES

MHC II

SARS vaccine development strategiesSARS vaccine development strategies

Targeting Nab induction Speed: Slow Safety: yes Efficacy: Partial

SCoVgene

SCoV protein/ glycoprotein

Subunit

Translated SCoVprotein sequence

1

9762

Epitope-rich frag- ment selection

Vaccine cocktail formulation

Targeting NAbs & CMI induction Speed: fast Safety: safest Efficacy: most expected

Multi-epitopedirected

SCoV

Inactivated SCoV

Heat/Chemicaltreatment

Targeting NAbs induction by Speed: SlowSafety: QuestionableEfficacy: Questiona- ble

InactivatedVirus

Attenuated SCoV

Tempe- raturetreatment

SCoV

Targeting NAbs & CMI inductionSpeed: SlowSafety: leastEfficacy: Question- able

AttenuatedVirus

rAdenovirus

SCoV protein/ glycoprotein

Targeting NAbs & CMI inductionSpeed: fastSafety: questionableEfficacy: questiona- ble

Live-virusExpression

Vector

SCoV gene

Development of modern day vaccines

Period Vaccine

Attenuated Killed 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 B20th century Measles Rabies Pneumonia

Mumps Miningitis Rubella

21th century FMD (UBI Asia) SARS ? (UBI Asia)

Immuno-informatics

In vitro validation

Vaccine Candidate

SARS Genomes

Potential epitopes

Validated epitopes

Prototype Vaccine

Pre-clinical Testing

Peptide constructdesign

Binding assaysT 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

from Genomics Genomics to UBIA’s SARS Vaccine UBIA’s SARS Vaccine