Success still eludes HIV vaccine attempts

Success still eludes HIV vaccine attempts
Comment E-mail Print Share
First Published: Mon, Nov 30 2009. 10 02 PM IST

Updated: Mon, Nov 30 2009. 10 02 PM IST
When researchers announced in September that an experimental vaccine tested in Thailand showed 31% protection against HIV, arguably the most dreaded bug to have surfaced in the past half century, it was a cause for celebration. It was the first positive result in a 20-year global effort towards a vaccine for HIV, even if it partially prevented only two strains, B and E, of the virus.
Still, a breakthrough remains elusive for the HIV vaccine project—the third most prolonged vaccine project in the world after polio and malaria, and ranking top in terms of investment and spread of efforts. The International AIDS Vaccine Initiative, or IAVI, the largest organization supporting a worldwide move in this space, alone has an annual budget of at least $200 million (Rs930 crore).
India, which has the third-largest HIV-infected population, has had its share of failed vaccine results. It’s now focusing on a new, early trial of a vaccine in humans, being conducted under the aegis of the Union government through the Indian Council of Medical Research (ICMR), the National AIDS Control Organisation (Naco) and IAVI.
Also Read Road To Prevention (Graphics)
The vaccine is a combination of two candidates—TBC M4 and Advax. In this approach, one vaccine candidate (a prime) is administered first, followed by a second candidate (the boost).
In the recent past, two vaccine candidates, tgAAC09 and TBC M4, were tested as independent candidates by two ICMR institutions—the National AIDS Research Institute (Nari) in Pune and the Tuberculosis Research Centre (TRC) in Chennai, respectively. Both fell short of expectations.
Nari’s trial was put on the back burner after it failed to generate adequate immunogenicity data; TRC’s TBC M4 showed a certain amount of safety and tolerance in patients, but didn’t do well on the efficacy parameter then. Immunogenicity data, in an early trial, is needed to determine the proper dose of the vaccine or drug to take the test forward.
“The unfortunate part is that there is no satisfactory result yet known to combat type-C HIV virus, which is found in India,” said Suresh Jadhav, executive director, quality control, Serum Institute of India Ltd, and president, Developing Countries Vaccine Manufacturers’ Network, India.
India’s latest initiative, though, looks promising. Rajat Goyal, country director of IAVI in India, said studies have shown that the combination approach has the potential to induce different types of immune responses and enhance overall response obtained by the use of either type of vaccine alone.
“It is expected that this prime-boost strategy would increase both the magnitude—a little bit like the height of a protecting wall—of the immune responses and their breadth—the thickness of the wall. This study is still ongoing, so (we) don’t yet know if this prime-boost combination has had an impact on the immune responses elicited by the vaccine when tested alone,” Goyal said.
IAVI plays a critical role in advancing novel vaccine approaches from concept to trials, besides financing and managing cross-national research partnerships to identify, develop and test promising AIDS vaccine candidates focused on the needs of the developing world.
S.M. Mehandale, a senior scientist at Nari, said India’s combination vaccine, being tested on 32 volunteers, is in the initial phase. “So a prediction of the success is still far away.”
The vaccine path has proved slippery particularly because the virus has a dynamic mutation pattern and scientists do not have appropriate animal models for pre-human studies. Still, about 40 different clinical trials are currently on globally for an AIDS vaccine. Most of them are combination vaccines as single-strain candidates don’t elicit a good patient response.
Parallel initiatives
IAVI, along with India’s department of biotechnology and the ministry of science and technology, developed the Indian Medicinal Chemistry Programme in 2007 to address a major obstacle in HIV vaccine development—the design of candidate vaccines to elicit neutralizing antibodies against HIV. “The initiative comprised top Indian and US scientists, and aims to accelerate the pace of HIV vaccine discovery by developing creative concepts for the next generation of HIV vaccines,” said Goyal.
According to him, the programme complements the work of IAVI’s Neutralizing Antibody Consortium, which is a global effort to develop AIDS vaccine candidates that can elicit broadly neutralizing antibodies capable of preventing HIV infection. Incidentally, there is no private sector initiative in India at present.
“As the investment that is required for setting up the kind of laboratories that can manage HIV virus is huge, no company will be able (to) take that risk unless they are completely sure of a research candidate that will work,” said Jadhav.
Still, an earlier agreement between IAVI and the Serum Institute to license any successful technology for manufacturing an HIV vaccine in India still exists. IAVI had selected the Pune institute as suitable if it were to outsource the manufacturing of AIDS vaccines to India if a successful technology emerged.
Unfortunately, no technology that establishes at least 70% success rate is yet to be found in these initiatives the world over, Jadhav said. For vaccines, a 70% success rate in the trials is considered promising.
Meanwhile, a new study released early this year at the 16th Conference on Retroviruses and Opportunistic Infections in Canada showed that a microbicide, a vaginal gel code-named PRO2000, appears to be 30% effective when applied before intercourse. Researchers are now conducting a separate efficacy trial of this microbicide in South Africa, Tanzania, Uganda and Zambia. These trials, also supported by IAVI, are in the final stages and are expected to produce more effective data soon.
Graphics by Ahmed Raza Khan / Mint
Comment E-mail Print Share
First Published: Mon, Nov 30 2009. 10 02 PM IST