Vaccine trials on AIDS

Contents

• What is AIDS?• Need of AIDS vaccine• How might an AIDS vaccine work• Difficulty in developing AIDS vaccine• Organizations• Clinical trials• References

What is Aids?

• 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 AIDS vaccine?

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 AIDS vaccine…….

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 and combinations of vaccines with adjuvants that can boost immune responses.

Why is it difficult to develop an AIDS vaccine?

• 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 vaccine research.

• 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)

Clinical trials

tgAAC09 Vaccine The purpose of this study is to determine safety and

immunogenicity (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: Randomized Control: Placebo Control Endpoint Classification: Safety

Contd…………

Masking: Double Blind

Primary Purpose: Prevention

Eligibility

Age:18 - 50 Years

Gender: Both

Healthy Volunteers: Yes

Inclusion 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 pregnancy

Exclusion 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.

References

http://www.avert.org/aids-vaccine.htm http://clincaltrialsfeeds.org http://clinicaltrials.gov http://en.wikipedia.org/wiki/HIV_vaccine http://www.cgdev.org/section/search?q=aids+vaccine http://www.hvtn.org http://www.stepsstudies.com http://www.avac.org http://www.nari-icmr.res.in/