'IAVI supports a comprehensive approach to HIV'

[Guest guest]

'IAVI supports a comprehensive approach to HIV'

The recent collaboration of the International AIDS Vaccine Initiative

(IAVI) with the Department of Biotechnology (Ministry of Science and

Technology, Government of India) gives re-birth to hopes of an AIDS

vaccine. Dr Sonali Kochhar, Medical Director, IAVI, talks to Aashruti

Kak about their plans to crack the HIV virus.

What is IAVI's contribution to AIDS research in India?

Under a partnership between IAVI, the Indian Council of Medical

Research (ICMR) and the National AIDS Control Organisation, Ministry

of Health & Family Welfare, IAVI has established two centres of

excellence for AIDS vaccine clinical evaluation in India in

preparation for multiple Phase I trials. These were set up at ICMR-

affiliated institutes—the National AIDS Research Institute (NARI) and

the Tuberculosis Research Centre (TRC), Chennai.

India's first clinical trial of a preventive AIDS vaccine candidate

(Adeno-Associated Virus AAV vaccine -tgAAC09) began in February 2005

at the Vaccine Trial center at NARI. The vaccine targets the most

predominant subtype (HIV-1 subtype C) in India. 30 healthy volunteers

were followed up for 12 months post-vaccination. No safety concerns

were identified and the vaccine was found to be well tolerated. In

addition, a single administration of the vaccine at the doses

evaluated in this initial study elicited modest immune responses. The

trial was completed in December 2006.

Another trial of a preventive vaccine TBC-M4 (which consists of a

recombinant MVA targeting HIV-1 subtype C), was launched at the

Tuberculosis Research Centre, Chennai, in February 2006. For this

trial, 32 adult volunteers, not infected with HIV were recruited.

Initial data confirmed that the vaccine candidate was safe and well

tolerated. In addition, preliminary results indicated an encouraging

immune response. However, this is just one small step in the clinical

trial process, still at an early stage as final results are expected

in mid 2008.

IAVI also signed an MoU with the Department of Biotechnology in

February, 2007, under which, DBT and IAVI are co-funding and co-

sponsoring a new Indian Medicinal Chemistry Programme to complement

the work of IAVI's Neutralizing Antibody Consortium (NAC), which aims

at designing vaccines that elicit neutralising antibody responses

against HIV infection.

What are IAVI's strengths in research that will aid this

collaboration?

IAVI is a global non-profit, public-private partnership working to

accelerate the development of a vaccine to prevent HIV infection and

AIDS. Founded in 1996, IAVI researches and develops vaccine

candidates, conducts policy analysis, and serves as an advocate for

the field with offices in New York, Nairobi, Johannesburg, New Delhi,

and Amsterdam. IAVI supports a comprehensive approach to HIV and AIDS

that balances expansion and strengthening of existing HIV prevention

and treatment programmes with targeted investments in new AIDS

prevention technologies. As the world's only organisation focused

solely on the development of an AIDS vaccine, IAVI also works to

ensure a future vaccine will be accessible to all who need it.

Has IAVI tied-up with universities for this programme?

IAVI is collaborating with scientists from the International Centre

for Genetic Engineering and Biotechnology, New Delhi and the Indian

Institute of Science, Bangalore for the Indian Medicinal Chemistry

programme. These scientists bring enormous expertise in peptide and

protein design to the collaboration with IAVI, strengths that are

crucial to the rational HIV vaccine design strategy being pursued by

the NAC.

For the Phase I vaccine trial currently ongoing at TRC, YRG-Care, a

leading, internationally renowned Chennai-based NGO, working in the

field of HIV/AIDS, is assisting TRC with community liaison, advocacy,

pre-screening for the recruitment of volunteers, training in

voluntary counselling and testing of counsellors of the VTC training

of technicians and quality control support for the laboratory at TRC

and assessment of Hepatitis B, C and Syphilis samples from TRC for

the volunteers recruited in the Phase I trial. YRG Care project staff

also received extensive training along with the TRC project staff.

What challenges do you face while conducting AIDS research and how do

you tackle these issues?

AIDS vaccine trials are expensive and complex to conduct; both in

terms of manpower, technical expertise and logistics. It requires

close collaboration and support from the community, media,

politicians, policy makers and the scientific community in the

country.

In order to ensure that clinical trials progress smoothly, it is

necessary to ensure that there is an availability of sophisticated

immunology and virology laboratories, and trained personnel support.

Standard protocols and reagents should be properly utilised and the

trial site should be prepared well in advance. Adequate steps should

be taken to ensure that the approval process is efficient and

shortened, participants are fully informed and have given their

consent and that the organisation holding the trial follows good

clinical practices, standard operating procedures (SOPs), and has

good data management systems. There needs to be a constant presence

of community advocacy and the participation of volunteers who are

resolved of the scientific, ethical and feasibility issues.

Can you tell us how are you looking at distributing the vaccine, when

it comes through?

Given the potential challenges to introduce and adopt AIDS vaccines

in India, IAVI is learning form the experience of introducing other

vaccines into India including Hepatitis B, HPV, UIP. It will try and

generate better data and information, which are critical for decision-

making and generate political and financial support. We also need to

clarify roles of partners to be involved, including NGO and private

sectors, along with central, state, and local governments, which will

have an important impact on implementation of a vaccination

programme. Assessment of infrastructure needs to be done in advance

for delivering an AIDS vaccine, including opportunities to leverage

existing networks to capture significant synergies in HIV/AIDS

services. There also needs to be a secure political and financial

commitment, which is essential for the successful implementation of

an AIDS vaccination programme.

Not easy to research

HIV is a difficult virus to target and developing a safe and

effective vaccine requires overcoming several scientific obstacles,

such as:

• HIV infection is characterised by early integration of HIV

DNA, referred to as the provirus, into the DNA of the host cells that

it invades. This causes the viral genes to become a permanent fixture

in the infected cells and in the offspring of these cells. Once

integration occurs, complete elimination of HIV by immune cells is

highly improbable

• HIV replicates rapidly and by making errors of copy, changes

its genetic composition each time. It is not possible to predict

whether a vaccine which protects against one virus subtype will

protect against another subtype (although some scientific research

seems to indicate that this cross protection is possible)

• HIV destroys the immune system, the very system that is

supposed to work with a vaccine to protect the human body from

infection and disease

• HIV is a difficult target for neutralisation by antibodies,

which act as the first line of defence in the body and prevent a

pathogenic invasion of host cells. Its viral envelope glycoprotein,

which mediates attachment and entry into host cells, has two kinds of

receptor binding sites - conserved (with a fixed sequence) and

variable (with a changeable sequence). The conserved sites are hidden

in crypts. The highly variable sites are exposed. The antibody

producing B cells recognise the variable loops but not the conserved

sites. Hence, the antibodies which are generated do not have broad

protection against different HIV strains

• Most other vaccines have been developed by people who have

been able to overcome infection naturally. This has never been

observed in HIV infection in humans

• There are no good animal models for HIV/AIDS. Although animal

model data provides major conceptual insights and reassurance about

the safety of vaccines, only human clinical trials will inform

scientists about the vaccines safety, immunogenicity and efficacy

• Normally, it takes a minimum of 16-20 years to go from basic

science and design to the pre-clinical and clinical research process

and bring a vaccine to the stage of marketing. To combat the

epidemic, the endeavour is to compress the timelines for AIDS vaccine

development to 8-10 years. This can be done by accelerating the

development of new and innovative AIDS vaccine designs and

prioritising the best candidate vaccines for large scale efficacy

testing

• Trials have to be conducted in populations where the vaccine

is eventually to be used, in order to determine its efficacy against

the prevalent circulating HIV sub-types

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