Kenyans will now have to wait for a couple of months before the much anticipated AIDS vaccine trials in Kagemi takes off, following disappointing results of a different HIV vaccine trial conducted by Merck and Company.

The Kenya AIDS Vaccine Initiative (KAVI) research team has already written to local regulatory authorities informing them of the delay. In the communication they also explain that while the Merck and their vaccine are designed on the same concept, they are fundamentally different in other aspects. 

In an exclusive interview with The Horizon, the scientists said they are delaying the trials as a precautionary measure to understand the impact of the Merck’s results and how they inform their work.

“What we want to do is study the information of the Merck’s findings and see if they can provide valuable information before we can move on,” says Prof Omu Anzala, the KAVI Director.

Partnership for AIDS Vaccine Evaluation ( PAVE 100) Team, to which KAVI is a member, has too put on hold some of the planned vaccine activities in North America until early next year as they consider the full impact of the Merck vaccine failure to kill HIV.

Prof Anzala says the information gathered from the Merck study is going to help them understand several parameters such as how frequent they should follow-up their volunteers or if they will need to increase the number of volunteers for their trial.

“The failure by the Merck vaccine to elicit sufficient immune responses enough to kill the virus is going to help us investigate the Cytotoxic T lymphocyte (CTL) threshold that might be required to prevent infection,” explains Prof Anzala.

KAVI had just recruited sufficient numbers of volunteers for the Kagemi trial, and was about to start vaccination when Merck announced what scientists have described “profoundly disappointing development for the HIV vaccine field.”

Merck’s vaccine, which is sending ripples through the scientific community, was one of the most promising AIDS vaccine trial involving 3,000 HIV negative volunteers, who were at higher risk of HIV infection.

Recruitment of volunteers began in 2004 in nine sites-Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States.

Known as the STEP trial, the vaccine had moved to the critical Phase II stage of “prove-of-concept” or a test that would have established the vaccine’s ability to prevent HIV infection or reduce viral load.

The vaccine, MRKAd5 trivalent vaccine, was designed to stimulate the production of the immune system’s T-cells that are able to kill HIV infected cells.

The researchers were also keen to find out if the vaccine would reduce the amount of the virus in the body in people already infected or those who become infected.

This was never to be: it failed to prevent study subjects from HIV infection or reduce the viral load. About 13 months into the trial, 24 of the 741 volunteers who received at least one dose of the vaccine were infected with HIV, with 21 of the 762 volunteers in the placebo group getting infected as well.

Of those who received at least two doses of the vaccine, 19 out of 672 volunteers were infected with 11 out of 691 in the placebo group being infected. Although the infections are said not be due to the vaccine but the volunteers lifestyles, these outcomes sent panic among the researchers.

An independent Data Safety Monitoring Board for the STEP trial recommended “that vaccination be discontinued because the trial was not going to meet its efficacy endpoints.”

STEP trial investigators have since been directed to discontinue vaccinating volunteers in this study and to monitor them in accordance with the study protocol.

So how does this have bearing on the Kenyan vaccine? The Merck vaccine is a mixture of three components each made with a weakened version of recombinant adenovirus serotype 5 (rAd5), viruses known to cause common cold. This vaccine was therefore expected elicit what is called CTL responses against HIV sub-type B.

The vaccine being tested in Kenya is made of two vaccines – the DNA and rAd5- designed to elicit immune responses against HIV strains A, B, and C. This vaccine has been developed by the Vaccine Research Centre, an offshoot of America’s National Institute of Health (NIH).

Merck study, also using the rAd5, works to stimulate immune responses like the Kenyan vaccine. However they did not use DNA as a priming agent as is the case with one being tested locally.

Still, the similarity in the concept has left the Kenyan scientific fraternity wondering about the effect of this result on the KAVI vaccine.

Speaking to Horizon, Prof Anzala and Prof Walter Jaoko however said there was no cause to worry since the two vaccines were different in regard to their design and mode of delivery.

Unlike Merck’s vaccine, the KAVI vaccine is designed to elicit both CTL and antibodies responses. It further uses DNA vaccine for priming the immune system, with the rAd5 boosting it for better response. While the Merck vaccine elicits CTL responses, it lacks these other properties.

PAVE 100 Protocol Team issued a statement saying that their vaccine trial will continue “as there are substantial differences between the NIH’s Vaccine Research Centre and Merck vaccine candidates.”

In August this year, the vaccine being tested by KAVI returned impressive results in the preliminary stages of the trials. Qualities of T cell responses in terms of the magnitude and the breadth as recorded in the initial trials have been high compared to the Merck vaccine.

Some scientists even think the Merck vaccine is likely to register better outcomes if they use DNA as the priming agent as is the case with the KAVI vaccine.

For Kenya, the delay in starting the Kagemi trial is going to slow the process of vaccine testing in the country by a couple of months.

KAVI was to start last month vaccinating volunteers in what is known as Phase 2 trials, which was critical for a bigger study called Phase 2b PAVE 100 planned for early next year.

More than 3,000 volunteers from East Africa are expected to participate in this study. In Kenya, the PAVE trials are planned for Kisumu, Kericho, Nairobi, and Kilifi. Rwanda, South Africa, Zambia, and Uganda are other African countries going to participate as well.

Despite the setback occasioned by the Merck trial, financiers and advocates of an HIV vaccine remained optimistic.

Said Dr Seth Berkley, the President and Chief Executive Officer of International Aids Vaccine Initiative: “In science, failure is a teacher. The precise lessons of the Merck results will take time to decipher. But the called-off trial is far from the end of the line.”

Dr Berkley added that “although skeptics will now argue even more loudly that it’s impossible to create a vaccine gainst AIDS, I disagree.”

To him, something important is going to emerge from the over 30 or so vaccine candidates that are in various stages of testing.

“Scientists are already devising alternative approaches, such activating the antibody arm of the immune system rather than the T-cell arm, which was the basis of Merck’s vaccine and others.”

A press release from Merck and HIV Vaccine Trials Network shared similar confidence.
“While we are very disappointed that this vaccine candidate did not demonstrate protection, the data from this trial will provide critical insights into this diseases and future vaccine development,” said the statement.

Meanwhile, the rAd5 used in the construction of vaccines can neither cause common cold nor HIV infection. The virus is usually weakened to stop it from replicating, a prerequisite for disease development.

The three HIV genes –pol, nef, and gag- in the Merck vaccine were expected to stimulate the body’s immune system to generate HIV-specific immune response through the CD8 T-cells.

The latter are programmed to recognize and kill HIV infected cells. Integrating only three HIV genes in the vaccine ensures it does not replicate to infect the volunteers. Hence Merck and other scientists belief those who were infected during the trials were not due to the vaccine.