As the Americas face an epidemic of Zika virus ahead of the Rio Olympics, Dr Nicola Davies looks at what can be done to contain it.
Since the first reported case in Brazil in May 2015, the Zika virus (ZIKV) has gripped the world, causing varying levels of concern from apocalyptic forecasts to denial. The greatest worry has been the impact on pregnant women and their unborn children, with a growing body of evidence suggesting a link between ZIKV and babies born with microcephaly – a small head circumference often linked with brain abnormalities.
With the 2016 Olympic Games to be held in Rio De Janeiro, there have been fears for the safety of the athletes and spectators. Officials have assured the public that the area is safe, but have advised pregnant women to consider not travelling to the Games. Meanwhile, what is being done to control the virus?
Controlling the vector
ZIKV is a flavivirus primarily contracted through a mosquito bite from the Aedes species. Recent evidence suggests that Zika may also be sexually transmitted. While it was first discovered in Africa, the potential for it to spread to other parts of the world is limited only by the distribution of the Aedes mosquito, as demonstrated by the recent outbreak in South America. A mosquito can acquire the virus by biting an infected person, then ZIKV is passed to the next person via further mosquito bites.
A controversial technology is being explored to control the Aedes aegypti population through genetic modification – the presupposition being that, if the mosquito is not there, the virus cannot be transmitted. This initiative was well under way before the outbreak as attempts were being made to curb the infections of similar viruses carried by the species.
Oxitec, a company focused on the genetic modification of pest insects for population control, recently began the ‘Friendly Aedes aegypti Project’ by releasing genetically modified male Aedes aegypti mosquitoes into the wild. When bred in the lab, these males are fed tetracycline as larvae and develop a genetic dependence on the antibiotic. They are then released into the wild and flood the population, diluting the number of fertile wild males. When they mate with wild females, they produce offspring that do not survive without the antibiotic tetracycline they have been engineered to have an inherited dependence on.
In small-scale experiments, the population has been reduced by 90 per cent, and plans to expand the project area are in discussion. Hadyn Parry, CEO of Oxitec, said: “Controlling the Aedes aegypti population provides the best defence against these serious diseases for which there are no cures.”
While this may certainly reduce potential risks, the distribution of Aedes aegypti has been steadily increasing. There is also concern that the remaining 10 per cent of mosquitoes survived, which means that inhabitants of the test area remain at risk of ZIKV.
In a similar initiative, the gene-editing technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has proved effective in inserting genes into mosquitoes that drive their population down. This technology essentially copies a genetic code from one chromosome and embeds instructions in the genome to forcefully insert itself in the matching chromosome pair. This method has been dubbed ‘gene drives’ and, in tests for population control where a gene that is lethal to mosquito larvae is inserted, it has achieved a 99 per cent success rate.
By inserting the gene on a sex chromosome (the X or Y), the engineered portion of the gene could prove lethal to either males or females, allowing the insertion to be carried into the next generation. This gene-?slicing technology could improve the initiative already in use by Oxitec, potentially providing the means to eradicate Zika along with all viruses borne by the Aedes aegypti mosquito.
In the event that the entire mosquito population cannot be eliminated, the most effective means of combating ZIKV is through a vaccine. However, there is currently no FDA-approved vaccine to protect against the virus, and it takes years to engineer, test and gain approval. The UK government has allocated £1m to construct diagnostic tests for suspected cases of Zika and to develop effective treatments for the virus.
There are two different technologies in vaccine development. One relies on either a live or a dead strain of the virus. In the case of a dead strain, the virus cannot replicate or infect a person. When a live strain is used, the virus is weakened to initiate an immune response without causing severe symptoms, so that women considering conceiving could be vaccinated before there is potential danger to the foetus.
The second possible technology uses a synthesised DNA sequence as the inoculant and is known as a recombinant vaccine. To develop a vaccine of this kind, the part of the virus that elicits a strong enough immune response is replicated and injected into a healthy individual. This prepares the body’s immune system to fight the virus before it can replicate and infect the host. This technique does not take as long to develop as the live/dead strain virus vaccines, since the pathogen does not need to be cultured and deactivated once the virus protein responsible for antibody production has been identified.
Several pharmaceutical companies are using these technologies in efforts to develop a vaccine, but as yet none have passed the rigorous testing required to clear it for use. GlaxoSmithKline is conducting feasibility studies to determine whether one of its current technologies is suitable for developing a Zika vaccine, but even then it would take 10 to 15 years to make a vaccine available.
Traditional methods of developing and testing vaccines involve growing the pathogen and then dissecting it to study the body’s immune response to its different components. Reverse vaccinology uses the genetic information of a pathogen to research the same factors, without the need to cultivate the pathogen. Its genome is coded and analysed. DNA segments thought to be the most likely to carry code for proteins found on the outside of the cell or virus capsule are then isolated and synthesised. Such a technique has been used to develop a vaccine for serogroup B meningococcus, and applying it to create a vaccine for ZIKV could reduce the development period and could potentially provide a more effective cure.
It should also be possible to modify an existing vaccine for a closely related virus. The flavivirus group includes dengue, West Nile, chikungunya, yellow fever and ZIKV. Platforms that have already been developed for other viruses can be used as a foundation for a Zika vaccine. Sanofi, for example, has an approved dengue vaccine and is investigating the possibility of adapting it to cover ZIKV, which has 60 per cent of the same DNA.
Indian pharmaceutical firm Bharat Biotech claims to have developed and patented an anti-Zika vaccine called Zikavac. It is exploring two avenues – the use of an inactivated strain and a recombinant vaccine with surface antigens. The inactivated Zika vaccine is now undergoing animal trials, so it may still be years away from becoming a marketable product.
The advances that have been made in pharmaceutical research hold the key to the discovery of a vaccine for ZIKV. If the release time can be reduced from decades to years, or even months, the prospects for the people and unborn children of the Americas will be much brighter. However, there is still much we don’t know about Zika.