HIV Vaccines OverviewHIV Vaccines OverviewShaleena TheophilusShaleena Theophilus

DefinitionsDefinitions

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”

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 route5-7 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.

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 route5-7 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 vaccine

Measles, mumps, rubella, polio (Sabin vaccine), yellow fever

Inactivated or “killed” vaccine

Cholera, flu, hepatitis A, Japanese 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

HIVHIV

VACCINE

Treatment

Prevent Infection

Lower Initial Peak Viremia

Lower Set Point or Eliminate HIV

Stop Progression

preventive HIV vaccine: a vaccine designed to prevent getting infected from HIV.

Humoral immune system

preventive HIV vaccine: a vaccine designed to prevent getting infected from HIV.

Humoral immune system

Cellular systemCellular 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.

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 VaccinesPreventive HIV Vaccines

Beyond HIV 101Beyond HIV 101

Attachment and EntryAttachment and Entry

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www.dkfz.de/de/f020/groups/bosch/index.html

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HIV Genes Code Vaccine Targets

HIV Genes Code Vaccine Targets

Env: gp120 and gp41 Gag: internal structural and capsid

proteinsPol: three replication enzymes

Nef: interferes with host for survival of infected T-cells

Tat: transcription activator protein

Env: gp120 and gp41 Gag: internal structural and capsid

proteinsPol: three replication enzymes

Nef: interferes with host for survival of infected T-cells

Tat: transcription activator protein

HIV Vaccine StrategiesHIV Vaccine Strategies

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

Virus-like Particles / Pseudovirions

+/- Adjuvants

Combinations

Whole killed HIV

Live attenuated HIV

X

X(therapeutic history)

DNA VaccinesDNA 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.

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.

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.

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.

Viral Vector VaccinesViral Vector Vaccines

Adenovirus

Step StudyStep 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

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 VaccinesTherapeutic HIV Vaccines

HIV Vaccine StrategiesHIV Vaccine Strategies

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

Virus-like Particles / Pseudovirions

+/- Adjuvants

Combinations

Whole killed HIV

Live attenuated HIV

X

X(therapeutic history)

HIV Vaccine StrategiesHIV Vaccine Strategies

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

DNA

Peptides

Subunits

Live Vectors

Dendritic Cells

Virus-like Particles / Pseudovirions

+/- Adjuvants

Combinations

Whole killed HIV

Live attenuated HIV

X

X(therapeutic history)

Dendritic Cell VaccinesDendritic 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.

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 InfectionDendritic 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

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

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.

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

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.

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)

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.

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 TrialsCanadian 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

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

Canadian HIV Vaccines Plan

http://pubs.cpha.ca/PDF/P36/23414e.pdfhttp://pubs.cpha.ca/PDF/P36/23414f.pdf

Canadian HIV Vaccines Initiative

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

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 research2. Clinical trials (low & middle

income countries)3. Production facility4. Policy and regulatory capacity of

low & middle income countries5. Community, legal, ethical and

human rights issues in Canada and globally

1. Discovery and research2. Clinical trials (low & middle

income countries)3. Production facility4. Policy and regulatory capacity of

low & middle income countries5. Community, legal, ethical and

human rights issues in Canada and globally

Global Vaccines EnterpriseGlobal 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/

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/

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

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

Useful websitesUseful websites

Other useful websitesOther useful websites

www.iavi.org

www.hvtn.org

www.avac.org

www.iavi.org

www.hvtn.org

www.avac.org