HIV Vaccines Overview
Shaleena Theophilus
Definitions

vaccine: A vaccine is a substance stimulates an
immune response that can either prevent an
infection or create a resistance to an infection.

No vaccine is 100% effective! Most that are used in
North America are between 70 and 95% effective
Vaccines provide both an individual benefit and a public
health benefit.
“herd immunity”
Estimated Herd Immunity thresholds for vaccine preventable
diseases
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Disease
Diphtheria
Measles
Mumps
Pertussis
Polio
Rubella
Smallpox
Transmission
Saliva
Airborne
Airborne droplet
Airborne droplet
Fecal-oral route
Airborne droplet
Social contact
R0[N]
6-7
12-18
4-7
12-17
5-7
5-7
6-7
Herd immunity threshold
85%
83 - 94%
75 - 86%
92 - 94%
80 - 86%
80 - 85%
83 - 85%
^ - R0 is the basic reproduction number, or the average number of
secondary infectious cases that are produced by a single index case in
completely susceptible population.
Vaccine Type
Live, attenuated
vaccine
Disease
Measles, mumps, rubella, polio
(Sabin vaccine), yellow fever
Inactivated or “killed” Cholera, flu, hepatitis A, Japanese
vaccine
encephalitis, plague, polio (Salk
vaccine), rabies
Toxoid vaccine
Diphtheria, tetanus
Subunit vaccines
Hepatitis B, pertussis, pneumonia
caused by Streptococcus
pneumoniae
Conjugate vaccines
Haemophilus Influenza type B,
pneumonia caused by Streptococcus
pneumoniae
DNA vaccines
In clinical testing
Recombinant vector
vaccines
In clinical testing
HIV/AIDS Vaccine Mechanisms
HIV
Prevent
Infection
Treatment
Lower Set Point or
Eliminate HIV
VACCINE
Lower Initial
Peak Viremia
Stop
Progression

preventive HIV vaccine: a vaccine designed to prevent
getting infected from HIV.
Humoral immune system
Cellular system

therapeutic HIV vaccine: a vaccine designed to
boost the immune response to HIV in a person
already infected with the virus (immune based
therapy). Also referred to as an immunotherapeutic
vaccine.
Preventive HIV Vaccines
Beyond HIV 101
Attachment and Entry
www.dkfz.de/de/f020/groups/bosch/index.html
Immune Response
Prime Boost Strategy
Prime
Boost
HIV Genes Code Vaccine
Targets
Env: gp120 and gp41
 Gag: internal structural and capsid
proteins
 Pol: three replication enzymes

Nef: interferes with host for survival of
infected T-cells
 Tat: transcription activator protein

HIV Vaccine Strategies
 DNA
Virus-like Particles /
Pseudovirions
 Peptides
+/- Adjuvants
 Subunits
 Live
Combinations
Vectors
 Dendritic
Cells
X
Whole killed HIV
X
Live attenuated HIV
(therapeutic history)
DNA Vaccines

Instead of using the whole organism or its parts,
these vaccines uses the microbe’s genetic material!

The DNA is vaccinated and then the cells take up
this material. The cells secrete the antigens (a
molecule that stimulates an immune response) and
display them on their surfaces. In other words, the
body’s own cells become vaccine-making factories.
Viral Vector Vaccines
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HIV genes are put in a non-disease causing viruses
Viral vectors “transfect” the cell.
The cell generates and presents proteins.
The body responds to this as it does any other foreign substance
The aim is to get the immune system to recognize the HIV proteins
and prepare long-lived memory cells that will "remember" the HIV
proteins and act against the whole virus if a person later becomes
exposed naturally through high-risk behavior.
However, the body’s immune response to the viral vector, mutations of
the virus in the body and toxicity issues could limit effectiveness.
Adenovirus
Step Study

MRKAd5 HIV-1 gag/pol/nef, or trivalent, vaccine, is
based on adenovirus,

a common cold virus that has been modified so that
it cannot reproduce and cause a cold in humans. The
adenovirus is used as a vector, or a delivery vehicle,
to transport three synthetically produced HIV genes
into cells. These genes stimulate the body to
generate a potent cellular immune response to HIV,
producing an army of killer T-cells programmed to
recognize and kill HIV-infected cells
Therapeutic HIV Vaccines
HIV Vaccine Strategies
 DNA
Virus-like Particles /
Pseudovirions
 Peptides
+/- Adjuvants
 Subunits
 Live
Combinations
Vectors
 Dendritic
Cells
X
Whole killed HIV
X
Live attenuated HIV
(therapeutic history)
Dendritic Cell Vaccines
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Dendritic cells orchestrate the body’s immune response
They grab foreign bodies in the blood and present them to other
immune cells to trigger powerful immune system responses to
destroy the foreign invaders.
HIV infection normally hijacks these important immune system
responses and uses the dendritic cells to cross the mucosa and get
to the CD4 cells.
T Breinig, 2005
Dendritic Cell Vaccine in HIV-1 Infection
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Study from Barcelona, started in November 2006
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Our group has reported recently the first human trial of 4
therapeutic immunizations at six-week intervals with
autologous monocyte-derived dendritic cells (MD-DC) loaded
with heat-inactivated autologous HIV in 12 HIV infected
patients who had been receiving highly active antiretroviral
therapy (HAART) since early chronic infection.
www.Clinicaltrials.gov
Immune Response to a Therapeutic HIV Vaccine
Followed by Treatment Interruption in Patients
With Acute or Recent HIV Infection

This study will determine whether MRKAd5 HIV-1 gag/pol/nef
vaccine followed by treatment interruption can maintain viral
suppression in patients with acute or recent HIV infection.
www.Clinicaltrials.gov
Safety and Tolerability of and Immune Response
to LC002, an Experimental Therapeutic Vaccine,
in Adults Receiving Anti-HIV Treatment

LC002 is a novel HIV therapeutic vaccine containing a DNA
plasmid that codes for most of HIV-1's proteins. LC002 is a
unique vaccine in that it is given through topical administration;
this allows for Langerhans cells (immune cells located under
the surface of the skin) to pick up the vaccine and deliver it to
the lymph nodes, causing an immune reaction.
www.Clinicaltrials.gov
Study of the HIV gp120/NefTat/AS02A Vaccine
to Treat Individuals With Chronic HIV-1
Infection on Highly Active Antiretroviral Therapy
(HAART)
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The adjuvanted protein vaccine candidate consists of three
recombinant viral antigens: the envelope glycoprotein gp120
and two regulatory proteins, Nef and Tat. The latter are
expressed as one recombinant fusion protein, NefTat. The
antigens are formulated in the proprietary AS02A adjuvant. The
goal of this trial is to assess the safety and immunogenicity of
the gp120/NefTat/AS02A vaccine in HIV-1-infected individuals.
www.Clinicaltrials.gov
Canadian Trials
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Remune® is a therapeutic vaccine made from whole HIV
particles stripped of the envelope layer and sterilized. It is used
to mimic an infection to boost the immune system. The dead
virus is emulsified in an adjuvant called "incomplete Freund's
Adjuvant" (IFA), a water and mineral oil mixture that helps to
stimulate the immune system.
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CTN 208
HAART alone or with Remune Vaccine followed by structured
treatment interruption in early HIV infection / observation of
recent HIV infection
CTN 203
Phase I/II Study of Remune® plus Amplivax™
CTN 173
Vaccination Before Treatment Interruption
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www.hivnet.ubc.ca
Canadian HIV Vaccines Plan
http://pubs.cpha.ca/PDF/P36/23414e.pdf
http://pubs.cpha.ca/PDF/P36/23414f.pdf
Canadian HIV Vaccines Initiative
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On February 20, 2007, Prime Minister Stephen Harper and Bill
Gates announced a partnership to fund the Canadian HIV
Vaccine Initiative. The project will encourage collaboration
between Canadian and international researchers and
institutions in the discovery, development, clinical trials and
manufacturing of vaccines within Canada for use globally. The
federal government is contributing up to $111 million to the
project, while the Bill and Melinda Gates Foundation will
provide additional funding in the amount of $28 million.
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Canadian International Development Agency
Public Health Agency of Canada
Industry Canada
Canadian Institutes of Health Research
Health Canada
1.
2.
3.
4.
5.
Discovery and research
Clinical trials (low & middle income
countries)
Production facility
Policy and regulatory capacity of low
& middle income countries
Community, legal, ethical and human
rights issues in Canada and globally
Global Vaccines Enterprise
The Global HIV Vaccine Enterprise is an alliance of independent
organizations around the world dedicated to accelerating the
development of a preventive HIV vaccine. The Enterprise was formed
in 2003 to coordinate scientific research and leverage funding to
speed the discovery of a safe and effective HIV vaccine. The
Enterprise was formally endorsed by the Group of 8 industrialized
countries (G8) in June 2004.
3 guiding principles:
1. Continue regular scientific assessments - to reflect lessons
learned, new opportunities and the influence of new discoveries
2. Establish a global process - standardization of data sharing,
communication, and convening must be established to optimize
progress at the global level.
3. Shared accountability - a culture of mutual accountability among
partners will be necessary for the effective implementation of the
scientific strategic plan.
www.hivvaccineenterprise.org/
Useful websites
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www.cdnaids.ca
Basics, advocacy updates
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www.aidslaw.ca
Discussion paper, info sheets,
HIV Vaccines and Human
Rights: Community Action Kit
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www.icaso.org
Primers
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www.hivnet.ubc.ca
Information on trials
Other useful websites
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www.iavi.org
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www.hvtn.org
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www.avac.org