R. Prasad

Its ability to elicit HIV-specific immune responses is modest

CHENNAI: The final results of Phase I Modified Vaccinia Ankara (MVA)-based AIDS vaccine trial conducted at the Tuberculosis Research Centre (TRC) here and made available exclusively to this Correspondent, show that the vaccine is safe. Its ability to elicit HIV-specific immune responses in the volunteers was modest.

“The vaccine has been found to be safe at both low and high doses. The results are very encouraging from both scientific and societal points of view,” said Dr. V.D. Ramanathan, TRC Deputy Director and the Principal Investigator of the trial.

Dr. Patricia Fast, Executive Director (Medical Affairs) of the International AIDS Vaccine Initiative (IAVI), who spoke to this Correspondent over telephone from New York, echoed similar sentiments.

The trial was conducted jointly by the Government of India — through the ICMR and NACO — and the not-for-profit IAVI, headquartered in New York.

The trial, using the MVA vector that contained six HIV genes, started in February 2006 and ended in February 2008. It involved 32 HIV-uninfected volunteers. They were split into two groups of 16 each. And in each group, 12 received the vaccine and four received a placebo (dummy). One group received low dose and the other, high dose.

The low dose tested was 5x10{+7} and high dose was 2.5x10{+8} (The Hindu, February 9, 2006).

Administered thrice

The vaccine was administered thrice — at the time of recruitment, one and six months after recruitment respectively.

They were followed up for one year after the last injection.

The number of volunteers who showed vaccine induced HIV-specific immune responses was encouraging. “The HIV-specific immune responses after all the three injections were administered were 82 per cent [9 out of 11 volunteers] with the low dose and 100 per cent [all the 12 volunteers] with the high dose,” Dr. Ramanathan said.

The immune responses after two injections were 73 per cent (8 out of 11 volunteers) with the low dose and 92 per cent (11 out of 12 volunteers) with the high dose.

“One volunteer who received the low dose left soon after taking the first injection,” said Dr. Ramanathan, explaining the difference in the number of volunteers in the two groups.

The trial showed that the TBC-M4 (MVA) vaccine was very unlikely to prevent HIV infection. “The neutralising antibody induced [to prevent infection] was very small,” Dr. Fast said.

That is precisely because the vaccine was designed primarily to elicit immune responses to reduce the viral load and hence delay the progression from infected to diseased state (AIDS), and to reduce the chances of the vaccinated person infecting others.

Apart from the number of volunteers showing immune responses, the level of immune responses produced is important to assess the efficacy of the vaccine.

“The strength and diversity of the immune responses were modest,” Dr. Fast said. “We don’t know how the modest response would translate to actual protection in people.”

But it appears that the MVA when used alone may not be able to elicit the best immune responses. A prime-boost vaccine strategy may be warranted.

“It may be possible to boost the [level of] immune responses when used in combination with other candidate AIDS vaccines. This is what the prime-boost trial aims to determine,” Dr. Fast said.

Efforts are on to start a prime-boost vaccine trial at the National AIDS Research Institute (NARI), Pune, and the TRC (The Hindu, August 11, 2008). The trial may start next year after getting the necessary regulatory approvals.

A prime-boost vaccine is necessary for another reason.

According to Dr. Fast, the persistence of immune responses of the MVA vaccine declined over several months. “But the MVA vaccine [tested at TRC] had better persistence compared to other MVA vaccines we have studied,” she said.

The longer the persistence of immune responses, the better was the ability of the vaccine to keep the viral load under check for a longer period of time. “Probably after the prime [dose] the immune response would last much longer,” Dr. Fast said.

She felt that the results obtained in this trial were promising and “challenges easily those published so far with other MVA-based IADS vaccine candidates.”

Though six genes were inserted into the MVA vector, the trial showed that most of the responses were produced by only two genes.

Previous vaccination

Unlike the Merck’s Adeno virus-based vaccine that made the volunteers more susceptible to HIV, the MVA vaccine tested at the TRC showed that previous vaccination did not cause any harm, and it did not interfere with the vaccine-induced immune response.

Dr. Sekar Chakraborty, Deputy Director of the National Institute of Cholera and Enteric Diseases, Kolkata, was responsible for producing the MVA vaccine construct that was used in the TRC trial.

YRC Care, Chennai, along with the TRC, was involved in recruiting the volunteers for the trial.