Spreading Knowledge is a great Legacy. MMG

1. Use of gene therapy to
manipulate Immune Response

2. • Prophylactic vaccination: before infection
• Therapeutic vaccination: after infection

3. Understanding immune response
1. To recognize ‘non-self’ foreign protein
challenge
2. To remove the invading pathogen
• Integration of all arms of immune system and
development of memory

4. Effector cells of the Immune system
• Originate in the bone marrow, naïve cells
leave the marrow and circulate the blood and
organs
• Mature and develop effector function upon
antigen challenge (some become memory
cells)
• All arms of immune system function in antigen
clearance, certain immune cells are
specialized for certain types of infections

5. Antigen Recognition
• Immune system requires antigen to be
presented in association with MHC in order to
be recognized as ‘foreign’
• Class I MHC (for CTL) presents epitopes
synthesized endogenously
• Class II MHC (for CD4 T-cell help) presents
epitopes taken up from cytoplasm or
extracellular space
• A vaccine must generate epitopes identical to
the natural infection

6. Protective vaccines enhancing protective
responses-Prophylactic Vaccination
• Vaccines enhance protective immune response
• Traditional vaccines: Live attenuated/ Fixed
inactivated
• New vaccines: Recombinant DNA protein (e.g.,
HbsAg)/ Peptide vaccines
• Gene vaccines: insert specific viral DNA to allow de
novo intracellular synthesis of viral proteins
• Naked DNA vaccines: direct injection of viral protein
genes
• Sustained low-level antigen expression-optimal Th-
cell response
• Combining DNA vaccines with booster doses of
vectors containing viral epitopes

7. Post infection Immunotherapy-
Therapeutic vaccination
• Enhance naturally occuring immune clearance
of infection
• Rarely done-immune response is usually
optimum and sufficient
• Inconclusive results for HIV-
immunosuppressed patients

8. Adoptive transfer of genetically altered
immune cells
• Good for immunosuppressed hosts after BMT
or OT
• CMV infection
• Failure of HIV clearance is based on CTL
‘exhaustion’-overwhelming antigen challenge
leads to inappropriate antigen specific T-cell
expansion and clonal cell death
• Artificial enhancement of antigen specific CTL

9. Cellular Immune responses to GT
Constructs
• Elimination of gene modified cells by immune
system: specific B/T-cell response against viral
vectors-major obstacle
• Use of gene therapy with immunosuppression-
systemic side effects
• Cellular immune response depends on type of
gene therapy construct
• Need for less immunogenic constructs