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

 Disease Transmission R0[N] Herd immunity threshold

 Diphtheria Saliva 6-7 85%
 Measles Airborne 12-18 83 - 94%
 Mumps Airborne droplet 4-7 75 - 86%
 Pertussis Airborne droplet 12-17 92 - 94%
 Polio Fecal-oral route 5-7 80 - 86%
 Rubella Airborne droplet 5-7 80 - 85%
 Smallpox Social contact 6-7 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 Disease

Live, attenuated Measles, mumps, rubella, polio

vaccine (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 In clinical testing

vaccines
 HIV/AIDS Vaccine Mechanisms
HIV

Prevent
Infection
Treatment

Lower Set Point or

VACCINE
Eliminate HIV

Lower Initial Stop

Peak Viremia 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 Combinations

 Live Vectors X Whole killed HIV

(therapeutic history)

 Dendritic Cells
X Live attenuated HIV
 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
 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 Combinations

 Live Vectors X Whole killed HIV

(therapeutic history)

 Dendritic Cells
X Live attenuated HIV
 Dendritic Cell Vaccines

 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

 Study from Barcelona, started in November 2006

 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)
 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
 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.

 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

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
 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.

 Canadian International Development Agency

 Public Health Agency of Canada
 Industry Canada
 Canadian Institutes of Health Research
 Health Canada
1. Discovery and research
2. Clinical trials (low & middle income
countries)
3. Production facility
4. Policy and regulatory capacity of low
& middle income countries
5. 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
 www.cdnaids.ca Basics, advocacy updates

 www.aidslaw.ca Discussion paper, info sheets,

HIV Vaccines and Human
Rights: Community Action Kit

 www.icaso.org Primers

 www.hivnet.ubc.ca Information on trials

 Other useful websites

 www.iavi.org

 www.hvtn.org

 www.avac.org