GlaxoSmithKline research head Moncef Slaoui explains how change of focus to cellular immunity was key to breakthrough
Moncef Slaoui was on holiday with his family when he heard the results of the first small trial, involving African infants, of the malaria vaccine he helped invent. It was a day he would never forget.
“It was 9 August 2004,” he said. “I’m on vacation with my kids, driving between Chicago and Indianapolis and my phone rings and it’s the team calling from Mozambique. I had to stop for at least an hour. I couldn’t drive any more. That was a big, big moment.”
The vaccine had been classed as around 55-60% effective. It was the first sign that Slaoui, now chair of R&D at GlaxoSmithKline, and his colleagues, were going to be successful in cutting the terrible toll of malaria in Africa. Halving the 200m cases a year would save lives and prevent a huge amount of harm.
It had been a long haul. Slaoui had joined the Belgian lab of what was to become GlaxoSmithKline 23 years ago with a background in immunology. “I brought a fresh perspective in what was then modern immunology,” he said. Some of his new colleagues had started work on a malaria vaccine but “it was more or less stalled conceptually”.
No one then had managed to make a vaccine against a parasite infection. Many in the scientific community thought it impossible. “We heard that a lot. There were many controversial discussions on whether we would be able to achieve success,” said Slaoui.
But his ideas drove the effort in a new and successful direction.
Scientists had been attempting to kill off the parasites injected by malarial mosquitoes as soon as they entered the bloodstream. But any vaccine attempting that has only minutes to work because the parasites quickly go to the liver, where the next stage of their life cycle occurs. After five days there is a burst of new parasites in to the blood cells and that is when the child falls ill.
Slaoui suggested using cellular immunity. “Rather than using antibodies that can kill bacteria or a parasite, we used T-cells that recognise [a] cell is not normal because it is infected by a parasite. It opened the opportunity to find the parasite where it [hid] in the liver and kill it there.”
It was easy to say, but hard to do. They needed to find the right adjuvant, a substance that would stimulate the immune system’s T-cells to mount a response against the malaria parasites.
It was in 1996, eight years after Slaoui joined the vaccine effort, that they became sure they were on the right track – during experiments in conjunction with the Walter Reed army medical centre in Washington DC.
Slaoui said: “It was the first demonstration of the proof of concept that we were able to make a vaccine that killed the parasite in the blood and also in the liver.”
The approach used would later be employed in GSK’s pandemic flu and cervical cancer vaccines, which would make money. Slaoui said GSK would not have dropped the malaria vaccine programme, which was solely for the benefit of people too poor to pay, but that the proftable spin-offs undoubtedly helped.
He said: “GSK Biologicals’ leadership was always totally committed to continue the work on the malaria vaccine for two equally good reasons. The malaria vaccine was a great vehicle to advance our platform of adjuvants for many other vaccines, [ones] that were more able to give us a return. But secondly there was truly a commitment to public health in general and our responsibility to society to make vaccines for those who would most benefit, even when they could not afford it.”
This was a stronger motivation in the vaccine community than in the pharmaceutical industry. He added: “Vaccines are associated with public health and the developing world and babies that you save from major infections, and therefore the idealistic motivation is very strong.”
It remained the case, he said. “Yesterday in Seattle [when the results were published] I was with some of the first core-team members – we all started together. It was very emotional.
