Download Khun Prasit Faipenkhong

Novel strategies for
prevention and treatment
of HIV infection
Prasit Faipenkhong
Pairoaj Vonghathaipaisarn
Rodjana Chunhabundit
Zhang Jianjun
Outline
•Introduction
•Interleukin-2
•Gene therapy
•Vaccines
•Summary
2
Introduction
•Problems with currently available
antiretroviral therapy
•only control not cure
•viral resistance
•drug-drug interactions
•adverse effects
3
Introduction
•Promising strategies for treatment or
prevention
•Interleukin-2
•gene therapy
•vaccines
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Interleukin-2
Interleukin-2 (IL-2)
•cytokine
•helper T cells (CD4+ T cells), cytotoxic T
cells (Tc, CD8+ T cells), natural killer cells
(NK cells)
•induce proliferation and differentiation of
CD4+ T cells and cytotoxic T cells
induce B cell proliferation, stimulate
macrophage activity, increase number and
toxicity of NK cells
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Interleukin-2 (IL-2)
•production is decreased in HIV infected
patients
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Aldesleukin
•a human IL-2 derivative
•absence of a N-terminal alanine,
replacement of cysteine with serine at
position 125, absence of glycosylation
•possess immunological activities similar to
those observed in native IL-2
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Aldesleukin
•has been approved by FDA for treating
metastatic renal cell carcinoma and
metastatic melanoma
•phase III clinical trials in HIV infected
patients
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Clinical aspect of aldesleukin
•Immunological benefits in several clinical
trials
increase CD4+ cells without sustained
increase in viral load
•Subcutaneous injection is similar to
intravenous infusion
improvement in immunological parameters
•Lower dosage (3 MIU/day) is still effective
increase CD4+ counts
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Clinical aspect of aldesleukin
•duration of intermittent therapy appears to
be important
•Adversely affects virtually every organ
system requiring aggressive supportive care
Flu-like symptoms
swelling, redness, or lumps
capillary leak syndrome (CLS)
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Gene therapy
Gene therapy in HIV
Ribozymes:
inhibit viral replication 10-1000 fold in
T-cells, and CD34 stem cell progeny (Phase I)
Transdominant mutant
cells transduced with vector carrying rev
M10 gene survived and expressed the
gene for longer time periods
Intracellular immunizations:
against tat, rev, reverse transcriptase
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Vaccines
Vaccines
•The need for HIV vaccine
high infection rate, high cost of
symptomatic treatment and drug therapy
to stop the global HIV pandemic
•Types of HIV vaccine
inactivated or killed vaccines, live attenuated
vaccines,subunit vaccines, live vector-based
vaccines, DNA vaccines
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Subunit vaccines
•Components of a pathogenic organism
•Advantages: stable, safe, defined
chemically and free from contaminate
proteins and nucleic acids
•Disadvantage: expensive, altered
conformation of antigenic determinants
•gp120
induce Ab in > 99 % of the subjects
phase III clinical trials
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Subunit vaccines
•gp160
broaden binding Ab response and boost
cellular immune responses
induce strong T cell responses against
a variety of HIV Ag
no evidence that gp160 has efficacy as
therapeutic vaccine in early stage HIV
infection
17
Live vector-based vaccines
•Live virus or bacteria vectors carrying
HIV gene
•Vaccinia-env, vaccinia-env/gag/pol,
canarypox-env,canarypox-env/gag
phase I or II
•Sustained expression of large amount of
HIV Ag, neutralizing Ab, CTLs responses
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DNA vaccines
•Research Findings
chimpanzees immunized with plasmids
carrying four HIV genes (env, rev, gag, pol)
can be protected against HIV infection
rhesus monkey immunized with plasmids
carrying only env gene can be protected
against HIV infection
•Human studies will be held in China at early
2001
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Summary
•interleukin-2: phase III
•gene therapy: phase I or II
•vaccines: phase III
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