HIV Vaccines and the Immune System (Nicole Frahm)
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Transcript of HIV Vaccines and the Immune System (Nicole Frahm)
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HIV Vaccines and the Immune
System
Nicole Frahm, PhD
HIV Vaccine Trials Network
Laboratory Program
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Immunology 101
Our immune system is able to recognize and fight
bugs that do not look like self
There are two parts of our immune system:
Innate: recognizes patterns on bugs, can fight them
right away
Adaptive: recognizes very specific parts of bugs but
takes a while to learn
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CD4+
T cell(helper)
Different arms of the adaptive immune
system
cellular humoral
CD8+
T cell(killer)
B cell
(antibodymaker)
Thibodeau GA, Patton KT: Anatomy and physiology,ed 7, St Louis, 2010, Mosby.
IgG
IgA
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Killing of target cells is very specific
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Antibody neutralization (IgG)
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Antibodies at the site of pathogen entry (IgA)
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Antibody-dependent cellular cytotoxicity
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Immunologic memory
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Vaccines take advantage of immunologic
memory
18th century: the observation that milkmaids are less
susceptible to smallpox suggests that exposure to
cowpox may protect from smallpox
Edward Jenner first inoculates
children with cowpox from
milkmaids and shows they are
protected, but other anecdotal
evidence existed previously
From georgiangentleman.posterous.com
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How do vaccines work?
The vaccine fools the body into thinking it has
been infected, so we will make a primary
immune response against the vaccine
Once the actual pathogen comes around, our
body responds with a secondary immune
response that is much faster and stronger
The correlate of protection has not been formally
defined for most vaccines, but protection is
believed to be antibody-mediated for most
licensed vaccines
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Can a vaccine induce both cellular and
humoral responses?
Different vaccine constructs are good at inducing
different responses:
Proteins are good at inducing antibodies
DNA vaccines are good at inducing CD4+ T cell
responses (but getting better for CD8+ T cells too)
Viral vectors can do everything, but it depends on
which virus they are based on:
Pox vectors induce primarily CD4+ T cells
Adenovirus vectors induce primarily CD8+ T cells
All virus vectors need to be boosted for good antibody
responses
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What else is important?
What parts of HIV go into the
vaccine
Antibodies can only see the
envelope protein on the incomingvirus, so envelope is essential for
neutralization
T cells can see all parts of HIV,
but some proteins seem to bebetter targets for T cells than
others
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So why do we not have a vaccine for HIV?
HIV is extremely variable
Between humans and apes, there is only 2-5% difference
in sequence between related genes, but
Different strains of HIV differ by up to 30% from eachother
Our immune system is very specific, and vaccine-induced
antibodies or T cells may not recognize a strain of HIV
that is very different from that used in the vaccine
The durability of the vaccine-induced immune
response wanes over time using current candidates
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How can we overcome this hurdle?
Current vaccines induce narrow and type-specific
immune responses
In the Step trial, a median of only one T-cell epitope was
recognized in vaccinees
Antibodies in Vaxgen recognized mainly the vaccine
strains
Two possible ways around: Increase the breadth of the vaccine-induced immune
response
Target regions that are conserved across most virus
strains (e.g. Gag for T cells, V2 or CD4 binding site for Ab)