HIV is a virus that gradually attacks immune system cells. As HIV progressively damages these cells, the body becomes more vulnerable to infections, which it will have difficulty in fighting off. It is at the point of very advanced HIV infection that a person is said to have AIDS
Each year around two million people die from AIDS related illnesses ,even a partially effective AIDS vaccine could save millions of lives
Efforts to develop a vaccine against HIV and AIDS have been underway for many years. Since 1987, more than 30 vaccine candidates have been tested
Research showing that: human antibodies can neutralise HIV in animal models9 ; some people have immune responses which are able to control the virus for years without developing AIDS; and vaccines are effective against mSIV in macaques10; aInaddition to generating antibodies they are able to stimulate cytotoxic T- cells, a type of lymphocyte which lacks the CD4 receptor HIV uses to enter the cell, and so cannot be infected by HIV. The normal role of these cells in the body is to control a viral infection and kill virus-infected cells before they divide. There is good evidence that these cells control the HIV during the first stages of infection, preventing the development of AIDS, often for many years. gProducts designed to work this way failed in clinical trials because the antibodies worked only against lab-cultured HIV, not against the wild strains of the virus.Other research has focused on encouraging the immune system to produce cells to fight HIV. Many scientists believe such “cell-mediated” approaches will not be very effective
Antigen: any substance that stimulates the immunesystem to produce an immune response. Antigens areoften foreign substances such as invading bacteria or viruses. Peptide: a short compound formed by linking two or more amino acids. Proteins are made of multiplepeptides. Pseudovirion: a virus-like particle that resembles a virus but does not contain its genetic information and cannotreplicate. In some viral diseases pseudovirions can interfere with infection by the real infectious virus.Adjuvant: a substance sometimes included in a vaccineformulation to enhance or modify the immunestimulatingproperties of a vaccine.
Between20-100 adults,PHASE II Between100-250 adults,Phase III Between 2500-20,000 adults , PHASE 1-Does the vaccine cause side-effects in humans?Does the human immune system respond to it?PHASE-2,PHASE-3-does it prevent HIV infection or does it delay progression to disease?K
hTheHIV Vaccine Trials Network (HVTN) is a non-profit organization which connects physicians and scientists with activists and community educators for the purpose of conducting clinical trials seeking a safe and effective HIV vaccine. Collaboratively, research professionals and laypeople The International AIDS Vaccine Initiative (known as IAVI) is a global not-for-profit, public-private partnership working to accelerate the development of vaccines to prevent HIV infection and AIDSVaxGen (OTCBB: VXGN) is a biopharmaceutical company based in the San Francisco Bay Area The National Institute of Allergy and Infectious Diseases (NIAID) is a component of the National Institutes of Health (NIH), which is an agency of the United States Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases The Division of Acquired Immunodeficiency Syndrome (DAIDS) is a division of the National Institute of Allergy and Infectious Diseases scientists have been conducting research to develop an HIV vaccine for nearly 20 years. The company also devotes extensive efforts to increase access to medicine
Dec2003vend –jan 2007
Follow up –for the planned duration of the study
Sponsors: Merck & Co. Inc. (Whitehouse, NJ) and the National Institute of Allergy and Infectious Diseases (NIAID) Endpoint Classification: Safety/Efficacy Study, primary purpose-treatment. After an initial HIV screening, confirmation of eligibility criteria and informed consent, participants were randomly assigned to receive three injections of either the study vaccine or a placebo vaccine
Start date- jan 2007,The trial was being conducted jointly by the South African AIDS Vaccine Initiative (SAAVI) and the NIAID-funded HIV Vaccine Trials Network (HVTN Ages Eligible for Study: 18 -35 Year,Genders:Both,Accepts Healthy Volunteers: Yes This study is currently recruiting participants. the HVTN 503 study also recommended that all volunteers be told whether they received vaccine or placebo and be strongly encouraged to return to their study sites for HIV risk-reduction counseling, protocol-related tests and for counseling about the possibility that those who received the vaccine might have an increased susceptibility to acquiring HIV infections
The trial recruited 16,402 young adults in Thailand. Ages: 18 -30, Genders:Both,Accepts Healthy Volunteers:Yes, Primary Purpose: Prevention Endpoint Classification: Efficacy Study,Study Start Date:October 2003,Estimated Study Completion Date: June 2009, sponsor-U.S. Army Medical Research and Materiel Command
and involved a total of six immunizations over six-months: four immunizations with ALVAC-HIV and two with AIDSVAX B/E given at the same time as the last two ALVAC-HIV injections. This combination of two different vaccines is called a prime-boost approach. In this approach, two vaccines are given in sequence with the goal of inducing the strongest and most comprehensive immune response
Vaccine trialson AIDS
Contents• What is AIDS?• Need of AIDS vaccine• How might an AIDS vaccine work• Difficulty in developing AIDS vaccine• Organizations• Clinical trials• References
• Aids stands for Acquired Immune Deficiency Syndrome• It is caused by HIV virus (Retrovirus) which attacks the immune system cells.• It is transmitted through bodily fluids ,sexual contact, sharing needles, mother to the baby.• Aids was first identified in the early 1980s.
Why do we need an AIDSvaccine? ?? Today, there are an estimated 33.4 million people living with HIV and AIDS• Children could be given an HIV and AIDS vaccine before being exposed to the HIV virus, and this would protect them from all routes of HIV transmission.• Vaccinating large numbers of people would be much simpler and cheaper than providing antiretroviral treatment for those already infected.
Is there an AIDS vaccine? No An AIDS vaccine does not exist yet.
How might an AIDS vaccine work?• It can be effective in two ways one can be therapeutic vaccine and other would be preventive vaccine.• An effective aids vaccine would teach the body to recognize HIV and provoke an immune response that would defend the virus if it entered the body.• The information on how to fight the immune system would become part of immune system’s memory and our body would be prepared to fight back.• Live attenuated and live-recombinant vaccines are able to fully activate the immune system
Approaches towards AIDSvaccine……. DNA vaccines: Synthetic copies of HIV genes are injected into the body resulting in the production of antigens that hopefully can produce a strong immune response. Bacterial and viral vector vaccines:• Copies of HIV genes are inserted into weakened bacteria or viruses that do not harm humans.• These bacteria or viruses carry the synthetic HIV genes into the body to induce an immune response.
Contd……Other approaches:It includes peptide vaccines, Pseudovirions andcombinations of vaccines with adjuvants that can boostimmune responses.
Why is it difficult to develop an AIDSvaccine?• HIV destroys the immune system cells that are meant to fight against it .• Soon after infection, HIV inserts its genetic material into human cells, where it remains hidden from the immune system.• HIV occurs in several subtypes, each of which is very different from the others.
Contd….• Even within each subtype, HIV is highly variable and constantly changing.• There are no good animal models to use in experiments although the use of non human primate (NHP) models could become a more significant model for HIV vaccine design and testing in the future.
Phases of Testing HIV Vaccines The three phases of HIV vaccine clinical trials are:• Phase I involves small number of healthy volunteers to test the safety of various doses.• Phase II testing generates additional safety data as well as information for refining the dosage and immunization schedule. The efficacy is tested in Phase IIb trial.• Phase III involves thousands of volunteers to test safety and efficacy.
Organizations sponsoring HIV vaccineresearch. • HIV Vaccine Trials Network (HVTN) • International AIDS Vaccine Initiative • VaxGen • National Institute of Allergy and Infectious Diseases (DAIDS). • Merck & Co.Inc • AIDS vaccine advocacy coalition (AVAC)
tgAAC09 VaccineThe purpose of this study is to determine safety andimmunogenicity (ability to induce an immune response)of a novel HIV vaccine based on adeno-associated virus(AAV).Sponsors: International AIDS Vaccine Initiative.Study Design :Allocation: RandomizedControl: Placebo ControlEndpoint Classification: Safety
Contd…………Masking: Double BlindPrimary Purpose: PreventionEligibilityAge:18 - 50 YearsGender: BothHealthy Volunteers: YesInclusion Criteria:• Healthy males and females.• Men or women between 18 -50 years of age.• HIV-uninfected and at low risk for HIV infection.• Available for follow-up
Contd……..• Literate, who can give written informed consent• Willing to avoid pregnancyExclusion Criteria:• HIV- infected or practicing high risk behaviour for HIV infection.• Pregnant or lactating women .• Presence of chronic disease, mental disorders and physical disability.• Recently received vaccine, blood or blood products.• History of allergic reactions to vaccination.
Contd……… Results :• In this trial ,HIV specific T-cell mediated immune response were observed.• However antibody response was not observed. Conclusion:• The trial was a benchmark in phase I clinical evaluation of HIV candidate vaccines in India.• The vaccine was generally well tolerated and raised no safety concerns.• The vaccine was found to be weakly immunogenic
List of clinical trials MRKAd5 HIV-1 gag/pol/nef :• Objective: This study is done to determine whether MRKAd5 HIV-1 gag/pol/nef vaccine followed by treatment interruption can increase immune system function in adults with acute or recent HIV infection who have started taking anti-HIV drugs.• This was a randomized, double-blind, placebo-controlled Phase IIb trial. Sponsor: Merck & Co. Inc. (Whitehouse, NJ) and the National Institute of Allergy and Infectious Diseases (NIAID)
Result:• The vaccine did not work. It did not prevent HIV infection and neither induce HIV-specific cell – mediated immunity.• It also did not reduce the amount of virus in the study participants who were infected..
The HVTN 503 (Phambili) HIV Vaccine• Objective: The HVTN 503 ("Phambili") study was designed to evaluate the safety and preliminary efficacy of the same Merck HIV candidate vaccine tested in the HVTN 502 STEP study, but it is being conducted in South Africa• This is a randomized, placebo-controlled, double-blinded Phase IIb trial
RV 144 (ALVAC / AIDSVAX )• Objective: The purpose of this study is to determine whether immunizations with an integrated combination of ALVAC-HIV (vCP1521) boosted by AIDSVAX gp120 B/E prevent HIV infection in healthy Thai volunteers.• This was a randomized, placebo-controlled, double-blinded Phase III trial.• Sponsor: U.S Army Medical Research and Material Command
What vaccines were used in the study?• ALVAC‐HIV (vCP1521) consists of a viral vector containing genetically engineered versions of three HIV genes (env, gag and pro). The ALVAC vector is a disabled form of bird virus called as canary pox.• AIDSVAX B/E is composed of genetically engineered gp120. Result:• The vaccine regimen is safe and 31.2 % effective at preventing HIV infection.• While this is a modest level of efficacy, it represents a major step forward for HIV vaccines, providing the first evidence that development of a safe and effective preventive HIV vaccine is possible.