Upload
medicineandhealthusa
View
2.502
Download
3
Embed Size (px)
Citation preview
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
www.dkfz.de/de/f020/groups/bosch/index.html
Prime Boost StrategyIm
mu
ne
Res
pon
se
Prime Boost
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