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Megan Clark
SUID 4830360
HB 146
10/30/03
Outline of Presentation
“DNA/MVA Vaccine”
Slides (1-10)
1. Quick review of biology of HIV transmission and replication (visual diagram)
2. 2 main vaccine approachesi
a. Neutralizing Antibodies (Humoral Immunity) – block HIV bonding to CD4
b. Cellular Immunity – killer T-cells destroy infected helper T-cells
3. Discovered b/c some Kenyan sex workers seem naturally immune to transmission despite
high exposure.ii – Rowland-Jones
a. Linked to HIV-specific cytotoxic T lymphocytes (CTL)
4. How their immunity works:
a. CD8+ killers destroy CD4+ cells infected by HIV, so virus can’t replicate and
infect others. (visual diagram)
5. Vaccine modeled after this natural immunity – induce high levels of HIV-specific CTLs
a. Investigators: UK Medical Research Council, University of Oxford – McMichael
and Hanke iii
b. Content of vaccine
i. DNA: consensus clade A gag p24/p17 and a string of clade A-derived
CTL epitopes
ii. +/- MVA vector: poxvirus modified vaccinia Ankara (MVA)
6. How vaccine works
a. Not quite clear on this part yet. Any suggestions on good sources?
7. Results:
a. Mice – strong T cells-mediated immune responses, at least 155 days
b. Rhesus macaques – prime-boost elicited HIV-specific T cell responsesiv
c. Humans – Phase I and Phase II trials underway in Oxford and Nairobi
i. Preliminary Oxford data – both vaccine components alone induced T cell
responses in majority
8. Will the vaccine work?
a. Analysis of data
i. Do the results support findings?
ii. Are the CTL assays good indicators?
b. Does the vaccine need to induce mucosal immunity to fully protect?v
c. Sex workers lost immunity after stopped working  prolonged exposure
required?vi
9. Will the vaccine be globally applicable?
a. Protect from different strains?
b. Economic feasibility?
10. Future outlook
a. When will phase III trials, drug to market?
b. Other cellular immunity vaccines in trialsi
i. alphaviruses
1. Semliki Forest Virus (SFV), Venezuelan Equine Encephalitis
(VEE)
2. pros
a. high expression of foreign genes
b. boostable (no anti-vector immunity)
3. cons
a. not as effective as MVAvii
ii. adeno-associated viruses (AAV)
1. persistent immunity following a single immunizationviii
Sources
International AIDS Vaccine Initiative. “IAVI R&D Agenda in Detail.”
http://www.iavi.org/vaccinedev/agenda.htm.
ii
Rowland-Jones S, et. al. The role of cytotoxic T-cells in HIV infection. Dev Biol Stand.
1998;92:209-14.
iii
Hanke T, et. al. Development of a DNA-MVA/HIVA vaccine for Kenya. Vaccine. 2002 May
6;20(15):1995-8. Review.
iv
Amara RR, Villinger F, Altman JD, et al. Control of a mucosal challenge and prevention of
AIDS by a multiprotein DNA/MVA vaccine. Science 2001; 292:69 74.
v
Evans DT, et al. Mucosal priming of simian immunodeficiency virus-specific cytotoxic Tlymphocyte responses in rhesus macaques by the Salmonella type III secretion antigen delivery
system. J Virol. 2003 Feb;77(4):2400-9
v
Vazquez-Blomquist D, Quintana D, Duarte CA. Modified Vaccinia Virus Ankara (MVA)
priming and Fowlpox Virus booster elicit stronger CD8+ T cell response in mice against an
HIV-1 epitope than DNA-Poxvirus prime-booster approach. Biotechnol Appl Biochem. 2003
Oct 23
vi
“Prostitutes Not Actually Immune.” BBC News On-line.
http://news.bbc.co.uk/1/hi/health/619316.stm.
vii
Xin KQ, Urabe M, Yang J, Nomiyama K, Mizukami H, Hamajima K, Nomiyama H, Saito T,
Imai M, Monahan J, Okuda K, Ozawa K, Okuda K. A novel recombinant adeno-associated
virus vaccine induces a long-term humoral immune response to human immunodeficiency
virus. Hum Gene Ther. 2001 Jun 10;12(9):1047-61.
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