HIV Vaccines Overview mumps

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					HIV Vaccines Overview
   Shaleena Theophilus
   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

   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
Conjugate vaccines      Haemophilus Influenza type B,
                        pneumonia caused by Streptococcus
DNA vaccines            In clinical testing

Recombinant vector      In clinical testing
   HIV/AIDS Vaccine Mechanisms


                                  Lower Set Point or
                                   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
Preventive HIV Vaccines

    Beyond HIV 101
Attachment and Entry
Immune Response    Prime Boost Strategy

                  Prime        Boost
    HIV Genes Code Vaccine
 Env: gp120 and gp41
 Gag: internal structural and capsid
 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 /
 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.

                   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 /
 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.

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.

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.

 Study of the HIV gp120/NefTat/AS02A Vaccine
    to Treat Individuals With Chronic HIV-1
Infection on Highly Active Antiretroviral Therapy
   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.

              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

Canadian HIV Vaccines Plan
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
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.

               Useful websites
      Basics, advocacy updates

      Discussion paper, info sheets,
                        HIV Vaccines and Human
                        Rights: Community Action Kit

       Primers

   Information on trials
         Other useful websites