Outbreaks of mosquito-borne dengue fever have attained near epidemic status in metropolitan São Paulo, prompting Brazilian researchers to rush forward the development and approval of a vaccine for the disease that has been developed in partnership with the US National Institutes of Health (NIH).
If Brazil’s National Public Health Surveillance Agency (ANVISA) approves it, new vaccine developed by Butantan Institute in São Paulo could be administered to the general population by 2016 – two years ahead of schedule. A plant capable of producing 12 million doses – and eventually enough to immunize Brazil’s entire population of 200 million – is planned.
Researchers believe a precedent has been established through the successful fast-tracking of a largely-untested ebola vaccine during the recent outbreaks in west Africa. This was used with success on western aid workers infected in the region.
The Butantan Institute already has more than 13,000 doses stockpiled, and hopes to take advantage of the current disease outbreak to test the vaccine’s efficacy across a broad population sample in a new and expanded phase three trial over coming months.
Following the long period of drought that caused water shortages in southern Brazil, the onset of the winter season has brought cool and damp conditions loved by the Aedes Egyptii mosquito. The open tanks used by residents to stockpile water during the dry months have also provided additional breeding grounds for the mosquito.
The result has been dengue outbreaks affecting over 340 per 100,00 inhabitants in the worst afflicted areas like the Pari urban district. Across Brazil’s most populous city, the average is 70 infected inhabitants per 100,000. With over 8,000 confirmed cases by mid April – a rise of 150% over last year (when dengue became a topic of anxiety for tourists visiting Brazil during the FIFA World Cup) – this is now the southern region’s top epidemiology issue.
By early May press reports indicated that more than 745,000 across Brazil had contracted the disease. The BBC reported that with 368 cases per 100,000 residents it amounts to an epidemic by World Health Organisation standards, but officials say the outbreak is not nationwide. More than half of the cases were in Sao Paulo.
While dengue is seldom deadly, press reports say there have been 67 fatalities across São Paulo state during 2015 – compared to 90 during the whole of 2014. Nationwide, however, the federal Health Ministry was claiming that that only 340 towns or cities were designated as being at risk of epidemic.
In São Paulo, early stage and second-stage clinical trials of the dengue vaccine using 300 volunteers have been going on since 2010.
Phase-two clinical trials are currently under way at the Butantan Institute and the University of São Paulo’s School of Medicine, with the aim of evaluating the vaccine’s safety and its capacity to induce a lasting immune response in volunteers.
But now Jorge Elias Kalil Filho, Director of the Butantan Institute, wants to fast-track the startup of third phase clinical trials. These were originally planned for late 2015.
Neuza Frazatti Gallina, coordinator of the project to develop the dengue vaccine and head of the pilot laboratory at the Butantan Institute, said the current capacity amounts to 500,000 doses per annum. A new plant being completed will initially ramp up annual production to 12 million doses, after which production will be raised in stages to cover the entire Brazilian population.
The challenge for developing a dengue vaccine that could be used not only in Brazil but across the region and in Africa, is that the vaccine must be quadrivalent, or able to protect against four serotypes of the dengue virus.
Research and development of the drug has been funded by the São Paulo Research Foundation (FAPESP). Its project named “Dengue: production of experimental batches of a tetravalent candidate vaccine against dengue,” is coordinated by researcher Isaias Raw.
According to The Butantan Institute’s Kalil, the initial immunological results are “highly promising”, as are the results of the first phase-one and phase-two trials performed in the United States by the NIH.
US-based researchers who are collaborating with Brazil include Donald Francis, University of California; Anna Durbin, Johns Hopkins University School of Medicine; and Steven Whitehead, NIH.
Researchers at the NIH originally developed and tested a liquid formulation of the vaccine, which remained stable for only four hours under refrigeration conditions. But with FAPESP’s support, Brazilian researchers managed to create a more stable vaccine using freeze-drying techniques, ensuring a 12 month shelf-life.
You can read a detailed article about this research by Brazilian journalist Karina Toledo by clicking here.