Nailing that elusive dengue vaccine
LYON – It has been a 20-year endeavour and the tests are still ongoing, but vaccine giant Sanofi Pasteur is so confident its dengue vaccine will work that it has already built a 300 million euro (S$504 million) plant to pump it out commercially.
It plans to have the world’s first vaccine for the mosquito-borne disease on the shelves by 2015, and has the capacity to churn out 100 million doses annually.
“We are now in the last step,” said Dr Guillaume Leroy, Sanofi Pasteur vice-president and dengue vaccine head, speaking at the production site in Neuville-sur-Saone in France.
“And we plan to go into all the countries where dengue is highly endemic.”
Trials so far have shown that the vaccine candidate is safe and protects effectively against dengue fever caused by three of the four dengue virus types.
The vaccine – which has been fast-tracked by the United States Food and Drug Administration (FDA) as it would address an important unmet medical need – is now being tested on more than 40,000 people in 10 countries. Results are expected next year.
Renowned dengue expert Duane Gubler, who has been studying dengue for 44 years, is optimistic.
“For the first time in my career, I think we’re near a stage in which we can control dengue as a major public health problem,” said Professor Gubler, who is with the Duke-NUS Graduate Medical School Singapore’s emerging infectious diseases programme.
“I didn’t think I’d live long enough to see this.”
Dr Roberto Tapia-Conyer, former Undersecretary of Health in Mexico and chief executive officer of the Carlos Slim Foundation, a non-profit organisation involved in developing public and social projects in Mexico and Latin America, said: “It’s a historic moment. There’s no question that we’re closer than ever to having a safe and effective vaccine against dengue.”
The next important step, he added, is to cut through red tape to make sure the vaccine is used where it is needed most.
Last year, dengue ranked as the fastest-spreading vector-borne viral disease with epidemic potential in the world, registering a 30-fold increase in disease incidence over the past 50 years, according to the World Health Organisation.
Dengue is also a leading cause of hospitalisation and death among children in endemic countries.
At Sanofi Pasteur’s gleaming new vaccine production plant, manufacturing is done at clean room standards.
“Just to enter the area, staff have a 55-minute preparation time because they need to put on two different types of garments, their whole body is covered and that’s all to protect the product,” said Mr Antoine Quin, director of Sanofi Pasteur’s dengue vaccine manufacturing site.
Producing the vaccine is a complex and time-consuming process involving producing cells, infecting them with a weakened form of the dengue virus and purifying the mixture.
Commercial production will begin at the end of the year, said Mr Quin, but it will take two years before the vaccine actually reaches the market shelves.
An earlier trial on 4,000 children in Thailand showed vaccine efficacy was 61.2 per cent against dengue virus type 1, 81.9 per cent against type 3 and 90 per cent against type 4. But serotype 2 eluded the vaccine.
Asked why the company is starting commercial production even before tests are finalised, Sanofi Pasteur’s Dr Leroy said he was confident the latest clinical trial would turn out good results.
“We got started even before the clinical trial finished. If not, we’d have to wait another five to six years after the end of the trial to be able to produce the vaccine commercially.”
Also, said Prof Gubler, the vaccine can be partially effective but still a “good tool” in the fight against dengue.
If a person is immunised against three strains, and is later infected by the fourth one, the illness will likely be mild, and the patient would not develop the more severe dengue haemorrhagic fever, he noted.
To be immunised, people would have to take three doses of the vaccine over one year (six months between each dose).
The cost of the vaccine has yet to be determined.
PROTECTION AGAINST 3 VIRUS TYPES
Dengue fever is endemic in more than 100 countries, and could reach record levels in Singapore this year.
Developing a new vaccine, however, can take many years and hundreds of millions of dollars.
Although several companies are testing potential dengue vaccines, it has so far been a long and arduous effort because there are four distinct, but closely related, serotypes of the virus.
So to immunise against dengue, four different vaccines need to be developed and delivered in one formulation, which then has to protect adequately against all four viruses.
The virus uses a specific “key” to get into the white blood cells to multiply.
But when the body creates antibodies to fight dengue, the virus is able to use these same antibodies as an alternative “key” to infect. Sanofi Pasteur’s vaccine, which is still being tested, is what is known as a live attenuated vaccine.
In such vaccines, the virus is weakened so that it cannot cause the disease, yet still remains able to produce an immune response.
So far, trials have shown that the vaccine candidate is safe, and protects effectively against dengue fever caused by three of the four dengue virus types.
The company is studying why there has been no protection against dengue serotype 2.
Source: The Sunday Times
Category: Features, Technology & Devices
