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ABSTRACTS FROM CURRENT LITERATURE
Year : 2008  |  Volume : 29  |  Issue : 2  |  Page : 107-110
 

HIV vaccine: Current trends and future perspectives


Department of Skin and V. D., Medical College and SSG Hospital, Vadodara, India

Correspondence Address:
Stuti Mahajan
Department of Skin and V.D., Medical College and SSG Hospital, Vadodara
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7184.48740

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How to cite this article:
Mahajan S, Sharma A, Marfatia Y S. HIV vaccine: Current trends and future perspectives. Indian J Sex Transm Dis 2008;29:107-10

How to cite this URL:
Mahajan S, Sharma A, Marfatia Y S. HIV vaccine: Current trends and future perspectives. Indian J Sex Transm Dis [serial online] 2008 [cited 2019 Nov 15];29:107-10. Available from: http://www.ijstd.org/text.asp?2008/29/2/107/48740


1) HIV Vaccine: Clinical Trials in India

In preparation for multiple Phase I trials, IAVI has established two centers of excellence for HIV vaccine clinical evaluation in India. The vaccine trial centers at NARI and TRC each have a data management unit and an immunology laboratory dedicated entirely to clinical trial activities.

The country's first clinical trial of a preventive HIV vaccine candidate began in February 2005 with an evaluation of safety and immunogenicity of tgAAC09 and because only a part of the HIV genetic material is used, this type of vaccine cannot cause HIV infection. They use an adeno-associated virus as vector. These adenoviruses naturally cause severe colds. After the infection is cleared the infected person develops antibodies specific to that adenovirus. Most people have previously been infected with Ad5. So pre-existing immunity to this vector posed a common problem with this vaccine.

In February 2006, researchers at the Tuberculosis Research Centre (TRC) in Chennai, Tamil Nadu, launched a Phase I trial of a second vaccine candidate, TBC-M4 (a modified vaccinia Ankara vaccine).

The trial was a double blind, dose-escalation, randomized, placebo-controlled trial. The total duration of the trial was approximately 24 months. The volunteers recruited for this trial were 32 healthy, HIV-uninfected men and women between 18 and 50 years of age, from all socio-economic strata. Three intra-muscular injections of TBC-M4 or placebo were administered to the volunteers.

Finally on 18 august, 2008, The Indian Council of Medical Research, the National AIDS Control Organization and the International AIDS Vaccine Initiative announced that the second Phase I AIDS vaccine clinical trial in India was successfully completed and indicated that the vaccine candidate had acceptable levels of safety and was well tolerated. The results suggest that further research is warranted. Currently, two additional Phase 1 trials testing the modified vaccinia ankara (MVA)-based candidate in a prime boost regime are planned for future and are under review by the relevant authorities in India and approved in UK.

  1. International AIDS Vaccine Initiative (2008, August 18). India Continues To Progress In AIDS Vaccine Development Efforts. ScienceDaily. Retrieved January 30, 2009, from http://www.sciencedaily.com­ /releases/2008/08/080817223650.htm
  2. IAVI in India www. info@iavi.org/view page.cmf


2) HIV Vaccine: Long term Non progessors

What can AIDS vaccine researchers learn from studying people who are HIV infected but progress more slowly to AIDS?

Some HIV-infected individuals are able to control the virus for much longer than a decade without ever taking antiretroviral treatment (ARVs). Researchers have even identified people who have been HIV infected for as long as 28 years and have never progressed to AIDS. These individuals are known as long-term non progressors, and they maintain very low viral loads and either don't progress to AIDS or do so much more slowly.

AIDS vaccine researchers are particularly interested in determining the type of immune responses that are responsible for slowing disease progression because mimicking these responses might be the key to produce an effective vaccine.

This could be especially true for a partially effective vaccine, one that would most likely not prevent HIV infection entirely but could lower viral load in people who do become infected. This lowered viral load would reduce the risk of them transmitting the virus to others, so a partially-effective vaccine could significantly reduce the number of new HIV infections.A team of scientists are now collaborating on a project to study specific subsets of long-term nonprogressors known as elite or viremic controllers.

Elite controllers are HIV-infected individuals not taking ARVs who maintain viral loads that are considered undetectable (<50 copies of virus per ml of blood). About 1 in every 300 HIV-infected people is considered an elite controller. Viremic controllers are infected people not taking ARVs whose viral load remains below 2000 copies/ml of blood.

They plan to analyze the immunologic and genetic characteristics of these individuals utilizing the information collected by the Human Genome Project that successfully mapped the thousands of human genes. By comparing this information across a larger cohort of controllers, researchers are hopeful that they will be able to identify the specific genes or immune responses that allow some people to control their HIV infection. Hopefully this will yield important clues for the future design of AIDS vaccines.

Its Deciphering AIDs vaccine, an Anthology of VAX and IAVI report articles explaining key concepts in AIDS vaccine research and clinical trials; By Kristen Jill K; www.iavireport.org.

3) AIDS vaccine for adolescents

As HIV continues to infect millions of people throughout the world, more and more of the newly infected are between the ages of 15 and 24. Despite this, AIDS vaccines have so far not been tested in adolescent volunteers.

But before AIDS vaccine trials with promising candidates can be initiated in adolescents, researchers must tackle potentially thorny legal, ethical, and regulatory issues, and make sure they adequately address the concerns of parents about their children participating in research.

Many organizations are currently working to develop guidelines and protocols that will enable future trials to be conducted successfully with adolescent volunteers.

Young women in South Africa continue to be at very high risk of HIV infection, with studies showing that HIV prevalence rates approach 16% among girls between age 15 and 24, four times the infection rates seen in boys of the same age.

Results from HPV and HBV vaccine trials also give researchers good reason to be optimistic that adolescents may respond even better to vaccination than adults.

For AIDS vaccine candidates it may therefore be necessary to run large efficacy trials in adolescents. It is unlikely that these can only be done in the US since HIV incidence rates there are generally too low among adolescents to support a conclusive Phase III trial, Researchers in South Africa and Botswana are leading the charge due to the high prevalence of HIV infection among adolescents in these countries.

The South African AIDS Vaccine Initiative (SAAVI) is currently collaborating with the HIV Vaccine Trials Network (HVTN) to prepare a protocol for an adolescent trial. Merck is now considering testing its lead vaccine candidate in adolescents. Adolescents may be uncomfortable disclosing their potential risk behaviors to a parent or guardian. This may become even more complicated in efficacy trials, where enrollment is dependent on the volunteer being sexually active and therefore at some risk of HIV infection, Another concern for parents when making the decision to allow their child to participate is the potential that volunteers in AIDS vaccine trials may test positive on HIV tests without actually being HIV infected.

Preliminary research indicates that many adolescents are eager to participate in AIDS vaccine research and the most common reason given for participation was the perception that it would offer them protection from HIV infection. This raises the concern of behavioral disinhibition in trials, where volunteers feel a false sense of protection from a vaccine candidate that hasn't yet proven effective.

Deciphering AIDS vaccine an Anthology of VAX and IAVI report articles explaining key concepts in AIDS vaccine researchand clinical trial; By Kristen Jill K; www.iavireport.org.

4) An HIV vaccine: Prime boost approach

Current approaches to vaccine design are cell mediated Immunity (T cell based Vaccine) and Neutralising antibodies. Current vaccines are classified as DNA Vaccines (HIVA, VRC4302), Recombinant viral vector Vaccines (ALVACvCP205, AIDSVAXB/B), Recombinant protein subunit Vaccine (Neftap + gp120W61D) and Prime Boost Approach (DNA/MVA, DNA/Protein subunit).

Future approaches to vaccine design are Mucosal immunity, Recombinant vectors, Virus like particles, Live attenuated vaccines, Whole inactivated viral vaccines, Synthetic peptide immunogens, Gene therapy, Antisense oligonucleotides.

Only one T-cell vaccine, Merck's MRKAd5 HIV-1 gag/pol/nef trivalent vaccine, has been tested, in two efficacy trials. The first referred to as the STEP trial was conducted in North America, South America, the Caribbean, and Australia; the second, called Phambili was conducted in South Africa. Both trials were terminated ahead of schedule when data from the STEP trial showed that the vaccine failed to prevent HIV infection and failed to lower virus levels in vaccinated volunteers who became infected. Unexpectedly, post hoc analyses of the STEP trial also found a trend toward a greater number of new infections among vaccine recipients than among placebo recipients.

A particular study called HVTN 505-will use a DNA prime/rAd5 boost vaccine regimen developed by the Vaccine Research Center at the National Institutes of Health (NIH). Parts of this vaccine regimen are similar to the vaccine used in Step and Phambili. The results of HVTN 505 will help us to better understand and develop T-cell-based vaccines.

Prime-boost" is a way of combining two different vaccine candidates with the hope of getting a better response from the body's immune system than giving either vaccine candidate alone. In the late 1900s, an assessment of the 'prime-boost' vaccine concept was initiated with three candidate vaccine combinations in phase I/II testing.

One combination was chosen for further evaluation in a phase III trial, that is the ALVAC-HIV (vCP1521) 'prime' and AIDSVAX gp120 B/E 'boost'. The selection criteria were based on immunogenicity, postinjection reactogenicities, and manufacturing feasibility. ALVAC-HIV (vCP1521 is a recombinant canarypox vector vaccine that has been genetically engineered to express antigens of subtypes B and E HIV-1. AIDSVAX gp120 B/E is a bivalent HIV gp120 envelope glycoprotein vaccine containing a subtype E envelope from the HIV1 strain A244 and a subtype B envelope from the HIV-1 strain MN. The envelope glycoproteins are co-formulated and administered at an equal combined dose of each antigen.

This recombinant vaccine induces both T cells and antibodies and is now being tested in a large-scale clinical trial in Thailand; results are expected at the end of 2009. With the great need for an HIV vaccine, it is our hope that the efforts in Thailand, jointly with those of colleagues working in other countries, will bring us all closer to that goal. In India- in New Delhi, On 05 February 2009, The Indian Council of Medical Research (ICMR) announced plans to initiate a Phase I clinical trial to test a combination of two AIDS vaccine candidates, ADVAX and TBC-M4, in a prime-boost regimen.

  1. An HIV Vaccine - Challenges and Prospects; Margaret I. Johnston, Ph.D., and Anthony S. Fauci, M.D. http://content.nejm.org/ Volume 359:888-890, August 28, 2008, No 9.;
  2. IV/AIDS Preventive Vaccine 'Prime-Boost' Phase III Trial: Foundations and Initial Lessons Learned From Thailand, Supachai Rerks-Ngarm; Arthur E Brown; Chirasak Khamboonruang; Prasert Thongcharoen; Prayura Kunasol, AIDS. 2006; 20(11):1471-1479


5) World's first HIV neutralising antibody centre and state of the art laboratory for AIDS vaccine design

The International AIDS Vaccine Initiative (IAVI) will support the creation of a centre devoted exclusively to designing vaccine to prevent HIV infection.

The centre in collaboration with the Scripps Research institute (SRI), one of the world's largest independent and non profit biomedical research organisations, will be located at institute's premises in California.

The first of - its kind centre will comprise multidisciplinary scientific teams, and bring a critical mass of structural biologists, virologists, chemists, immunologists and computational biologists together to work side-by-side.

The centre will link to an expanded international scientific consortium, known as the Neutralising Antibody Consortium (NAC). The centre and broader NAC will collaborate closely with many levels of IAVI's research programme.

Antibodies that can effectively neutralise many different forms of HIV are referred to as broadly Neutralising antibodies. Unfortunately none of the candidates tested so far has been successful in inducing neutralising antibody response. This is one of the major scientific obstacle in the AIDS vaccine development.

In recent years, Researchers have successfully crystallised several broadly neutralising antibodies to HIV, determined their structures down to the atomic level, and used this information to get a handle on how each disables HIV. They are now applying what they have learnt to develop immunogens that, when delivered as vaccines, will reliably induce these antibodies in all people, with the goal of preventing HIV infection.

Regularly administration of adequate Neutralising antibodies into the humans would be impractical.So by introducing the gene for a broadly Neutralising antibody into a cell, Researchers are hopeful that body's own cells would coninuously produce antibody. Researchers are using Crippled Virus as a Vector to chauffeur the antibody genes into human cells.

Researchers are now conducting additional Pre clinical studies to try to determine what quantity of antibody needs to be produced to provide protection and their presence in mucosal tissues,which are primary entry point for HIV during Sexual transmission.

In addition to this, A new AIDS vaccine design and development laboratory - a state - of - the - art facility opened in NEW YORK city in November. IAVI"s Design Lab is the only facility in the world to be dedicated exclusively to the design and development of an AIDS vaccine and is housed within a planned new bioscience centre at the historic Brooklyn Army Terminal. The programmes at the lab will complement those IAVI has with both the private sector and academic partners throughout the world.

IAVI India Newsletter "SANKALP" vol. 7 (4) December 2008.




 

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