T-cell epitope vaccine design by Immunoinformatics

1. T-cell epitope vaccine design
by
Immunoinformatics
By
Hanif Alfavian

2. Introduction
Bioinformatics is the study of living systems through computation
1. Genome analysis
2. Transcriptome analysis
3. Protein/Proteome analysis
4. Systems Biology
5. Immunoinformatics
6. Genome-phenome mapping
7. Biodiversity Informatics

3. What is Immunoinformatics?
Computational systems biology of immune response
1. Genome screening - marker detection
2. Proteomics/genomics of diseased state
3. Sequence analysis of antigens/markers
4. Structure analysis of antigens
5. T cell epitope analysis
6. Antibody epitope analysis
7. Vaccine design

4. Types of vaccines
 Inactivated vaccines
 Live attenuated vaccines
 Subunit vaccines(hepatitis B)
 Virus-like particles
 Toxoid vaccines
 DNA vaccines
 Peptide vaccines

6. Properties of Epitopes
 They occur on the surface of the protein and are more flexible than the rest
of the protein.
 They have high degree of exposure to the solvent.
 The amino acids making the epitope are usually charged and hydrophilic.

7. T-cell epitopes
 Part of antigen recognizable by antibodies, B cells or T cells
 both foreign and self proteins
 conformational or linear structure

8. Epitope
T cell receptor
MHC

9. 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
TCR
MEMORY B CELL

10. 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

11. reverse vaccinology
 The methodology of analysing the pathogen genome to identify potential
antigenic proteins
 reducing time and saving resources
 Pathogens grow quickly, extraction of their proteins and then testing of those
proteins on a large scale is expensive and time-consuming

12.  the investigation of the binding affinity of antigenic peptides to the MHC
molecules is the main goal when predicting epitopes
 structure-based methods(three-dimensional structure of the proteins)
 sequence-based methods (analyse the amino acid sequence)