La pregunta del millón: ¿para cuándo una vacuna contra el zika?

The Million Dollar Question: When Will We Have a Vaccine Against the Zika Virus?

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[This article has been published in Spanish in El País - Planeta Futuro]

Since its discovery in Uganda in 1947, and until recently, infection with the Zika virus was considered to be a relatively mild illness, with symptoms similar to those of dengue fever but less severe. During the current Zika epidemic in Latin America, however, the infection has been associated with an increase in cases of microcephaly in newborn babies and of Guillain-Barré syndrome in adults. As a result, numerous national and international health institutions, working with specialised teams of scientists all over the world, have started a race against the clock in an effort to understand Zika virus disease—a condition practically unknown until recently—and to find ways to fight the problem.

The most optimistic forecasts anticipate that clinical trials in humans could be underway by the end of 2016

Today, the main strategies used to control the epidemic and reduce its impact on the health of affected populations are improving diagnosis and treatment of the infection, controlling Aedes mosquitoes (the insect responsible for transmitting the virus), and working to develop vaccines against the infection. While none of these strategies is considered totally effective in isolation, experts believe that the combination of all three will achieve adequate control of new epidemics. Of the three, controlling the mosquito population is the most effective intervention because in addition to reducing transmission of the Zika virus, vector control also reduces the incidence of other diseases transmitted by the same insect, including dengue and chikungunya. However, we do not have many tools that can guarantee durable and sustainable control of mosquito populations.

The most urgent need, besides developing economical and reliable rapid diagnostic tests, is to develop an effective vaccine capable of preventing the infection. In spite of a huge global effort launched in recent months to fast track Zika vaccine development, the most realistic forecasts consider that it will take from three to five years to obtain a vaccine that can be used to protect the population. Given the serious consequences of Zika virus infection during pregnancy, it is imperative to develop a vaccine that can safely protect pregnant women and newborn babies. Ideally, the vaccine should be effective after a single dose and offer lasting protection against different viral lineages.  The required characteristics are very similar to those of the vaccine against the rubella virus. In many respects, the problems caused by the Zika virus are similar to those associated with congenital rubella syndrome, which also gives rise to complications in newborn babies of infected mothers. In this regard, it is interesting to note that the Pan American Health Organization declared, in April 2015, that congenital rubella syndrome had been eliminated from the Americas, almost seventy years after its discovery.

At least 14 institutions with different initiatives all over the world are currently working towards the goal of developing a safe and effective vaccine

Existing scientific evidence relating to the development of effective vaccines against other viruses belonging to the same family, including the yellow fever and Japanese encephalitis viruses, may help to speed up the development of a Zika vaccine in the laboratory and in clinical phases.  The Zika effort can also take advantage of the work of the many teams of scientists who have been working to develop an effective vaccine against the dengue virus and the study platforms they have been using over the last decade. Similarly, an interesting approach used to fight cytomegalovirus infection may prove useful in cases of Zika infection during pregnancy:  immunoglobulin inoculation of the mother's blood could block the virus, thereby reducing the adverse effects of the infection and preventing complications in the newborn. One of the most important advances in recent months has been the development of a mouse model of Zika virus disease, which will make it possible to quickly assess the safety and efficacy of candidate vaccines.

Project sustainability is one of the most challenging aspects of the process

At least 14 public and private institutions with different initiatives all over the world are currently working towards the goal of developing a safe and effective vaccine against the Zika virus. The approaches most likely to succeed include the use of live attenuated virus, inactivated virus (similar to the approach used for yellow fever and Japanese encephalitis vaccines), the use of attenuated chimeric virus (similar to the dengue vaccine that uses the structure of the yellow fever virus), DNA-based vaccines, and recombinant DNA vaccines (see Table). One of the obstacles that will require particular attention in the development of a Zika  virus vaccine is the relationship between the infection and Guillain-Barré syndrome because an association between that syndrome and the swine flu vaccine developed in 1976 has been observed.  

A number of challenges must be overcome in the race to develop an effective vaccine against the Zika virus. The most optimistic forecasts anticipate that, for a few candidate vaccines, clinical trials in humans could be underway by the end of 2016. The vaccine development process includes a number of steps designed to ensure the safely and efficacy of the eventual product and this means that it is very unlikely that a definitive vaccine will be available during the current epidemic. If a candidate vaccine is successful it will be possible in the not too far distant future to prevent new epidemics. Project sustainability is one of the most challenging aspects of the process. The current support of international institutions and policies must be maintained, and adequate global funding measures must be put in place to ensure the continued research needed to gather more knowledge about this emerging disease.

Pedro Martínez de Salazar coordinates arbovirus research and the response to the Zika virus at the Barcelona Institute of Global Health (ISGlobal)

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