HIV Vaccines and the Immune System (Nicole Frahm)

8/4/2019 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)

HIV Vaccines and the Immune System (Nicole Frahm)

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