AIDS vaccine Chennai trial results encouraging

R. PRASAD
Thursday, Jan 24, 2008
http://www.hindu.com/seta/2008/01/24/stories/2008012450031600.htm
All in the high-dose group who got the vaccine showed immune response
The vaccine tested contains six HIV genes inserted into the MVA vector

The MVA vaccine construct used in the trial was developed by a Kolkata based scientist
There appears to be a greater possibility of finding an efficacious AIDS vaccine. The preliminary results of the
Phase I trial of the AIDS vaccine undertaken in Chennai have been largely encouraging.
The trial undertaken at the Tuberculosis Research Centre (TRC), using the Modified Vaccine Ankara (MVA) vector
has shown the ability to elicit immune response.

Unlike the three doses used at the National AIDS Research Institute (NARI) trial, Pune, the Phase I trial at TRC
involved just two doses — a high dose (2.5x10{+8}) and a low dose (5x10{+7}).
Vaccine safety
Much like the AAV vaccine tested at NARI, the vaccine tested at TRC has been found to be safe at both the doses.

But where the MVA has probably scored better compared with AAV, at this stage, is the number of volunteers who
received the vaccine recording an immune response.

“We have seen 75 per cent immune response [9 out of 12 volunteers] with the low dose and 100 per cent with the
high dose [all the 12 volunteers] after three injections,” said Dr. V.D. Ramanathan, Deputy Director (Department of
Clinical Pathology) at TRC and the Principal Investigator of the vaccine trial. The level of immune response seen,
among other details, will be known only after the final analysis of the data.

The immune response seen after just two injections were given to the volunteers was good.

According to Dr. Ramanathan, 66 per cent immune response (8 out of 12 volunteers) was seen in the low dose group
and 92 per cent (11 out of 12 volunteers) in the case of high dose group.

It may be recalled that vaccine trial at Chennai was started in February 2006 (The Hindu, February 9, 2006) and
involved 32 volunteers who were split into two groups of 16 each.

Of the 16 in each group, 12 received the vaccine and four received a placebo (dummy).
Final results
While the 18 months follow-up of the volunteers belonging to the low dose category has been completed, the
required follow-up of those in the high dose group will be completed in the first week of February 2008.

The first volunteer to be given the high dose was in the first week of August 2006.

The preliminary immunogenicity (immune response) result was presented during the AIDS vaccine conference at
Seattle. The final results will be available only in mid-2008.

So will there be a surprise in the final results? “How the immunogenicity will translate into actual protection
remains to be seen,” said Dr. Ramanathan. Dr. Patricia Fast, Executive Director (Medical Affairs) of the
International AIDS Vaccine Initiative, New York in an email communication to this Correspondent noted, “…We
expect that the [interim data result] is close to the final responses.”

Only Phase II and Phase III trials involving larger number of people would help in knowing this crucial issue.

“The results of the first trial suggest that further clinical research is warranted,” Dr. Fast noted. She also indicated
that the conduct of further clinical research will depend on the Indian Government.
The man behind
If the MVA vaccine has shown encouraging results in the Phase I trial, the full credit should go to the person who
was responsible for producing the MVA vaccine construct — Dr. Sekar Chakraborty, Deputy Director of the
National Institute of Cholera and Enteric Diseases, Kolkata.

Unlike the vaccine tested in Pune (AAV) that contained only three HIV genes put into the vector, the MVA has six
genes.

But it is not just the number of genes that has probably resulted in better immune responses. The six genes have
been put in two different positions of the MVA genome. This is unique and thus different from the other MVA
constructs developed by people abroad.

Dr. Chakraborty had also modified the natural amino acids of three of the six genes to enhance the immune
response. Dr. Fast noted that it is “…not yet possible to conclusively identify the reasons” for the good showing of
the MVA construct.
High stability
While the earlier MVA construct suffered from instability problems, the construct developed by him has been shown
to have 96 per cent stability.

This increased stability has been achieved by putting the six HIV genes in two different positions of the MVA
genome.