As Zika fear rises, especially in the wake of the World Health Organization last night declaring a state of public health emergency, people are inevitably asking why we don’t have a vaccine to protect against the mosquito-borne virus.
Zika is generally a mild illness, causing fever, rash and joint pain, which usually resolves within seven to ten days. It was originally restricted to small outbreaks in the Pacific islands, Southeast Asia and Africa.
Due to the previously low impact of the virus and the estimated US$160-500 million it costs to develop a vaccine, Zika vaccine has not been on the radar. Other severe and potentially fatal mosquito-borne diseases such as malaria, dengue, and West Nile virus affect millions of people each year and have been a higher priority.
That has all changed with the recent “explosive” spread of Zika in the Americas and the potential link with microcephaly (reduced head size and brain damage) in babies of pregnant women who were infected.
Now we’re playing catch up on the research needed to develop vaccines. We know very little about how Zika replicates, how it causes disease, or how the immune system protects against infection.
So what is the status of Zika vaccine development? And how does this compare with the other mosquito-borne viruses that continue to have such a devastating impact on the world’s health?
The ideal vaccine induces a strong response from the immune system, gives long-term protection with few doses, and causes no side effects. Though quickly developing such a vaccine is rarely this simple.
It’s early days, but scientists from the Public Health Agency of Canada, the Butantan Institute in Brazil, and the US National Institutes of Health have started work on Zika vaccines. These research teams may have vaccine candidates ready for initial clinical trials towards the end of the year.
Although full regulatory approval of a successful vaccine would take many years, it could potentially be used in public health emergencies within a year.
The yellow fever vaccine, developed in 1938, has been highly successful at protecting against the virus, which can cause bleeding, jaundice, kidney and liver failure and, ultimately, death. Of the 44 countries at risk of yellow fever in Africa and the Americas, 35 have incorporated Yellow Fever vaccines into infant immunisation programs.
It is a live vaccine, in which a “weakened” virus induces a protective immune response against subsequent infection.
Live vaccines generally give strong protection, but safety is a significant issue, particularly in people with a weakened immune system.
Dengue fever is a widespread tropical disease caused by dengue virus, which is transmitted by mosquitoes. Late-stage clinical trials of dengue vaccines are underway, and a vaccine has recently been licensed for use, but so far only in Mexico.
The field is littered with promising but failed vaccines that could not provide protection against the major strains of dengue virus. Nonetheless, there is hope that one will be available more widely in the coming years.
Chikungunya virus has recently emerged as a serious human pathogen, causing fever and excruciating pain in the joints that can last months.
As with Zika, chikungunya was long considered unimportant because of its limited geographic distribution. Its dramatic expansion over the past decade, particularly in Southeast Asia and the Americas, has led to mobilisation of the vast medical research capabilities of the United States in response to the threat of it becoming established there.
Chikungunya vaccine development is proceeding rapidly, with a number of vaccines entering clinical trials. Researchers have reported early successes, but we are at least several years away from getting an approved vaccine.
The big one is malaria, which kills more than 400,000 people a year. Scientists have been working on malaria vaccines for decades.
The RTS,S vaccine, developed by Glaxo Smith Kline, was successful in clinical trials and may soon be routinely used.
However, it only worked for some patient groups and provided only partial protection. Given its partial efficacy, there is debate in the medical community about the vaccine’s value.
The search continues for better vaccines.
Why is it so difficult to develop vaccines?
There is no recipe for the perfect vaccine. Despite the ever-increasing sophistication of vaccine technology, vaccine development often comes down to “suck it and see”. Many vaccines look promising in pre-clinical testing, only to fall over during the slow and expensive clinical trial process.
For many infectious diseases, we still don’t know what type of immune response is the most effective in providing protection. Since vaccines induce a protective immune response against infection, this can make vaccine design very difficult.
Vaccine safety is a major issue. “Live” or “attenuated” vaccines that involve a related or weakened version of the pathogen are often the most effective. But there is still the potential for these vaccines to cause disease, especially in recipients with weakened immune systems.
Vaccines go through a long process of clinical trials and assessment by regulators before they are approved for routine human use. This is a necessary process, but it sets a very high bar for approval. One of the most successful vaccines ever produced – the smallpox vaccine – is a live vaccine and would probably not have been approved by today’s regulators due to safety concerns.
For dengue, there is an additional complication. People previously infected with dengue are at risk of developing much more severe disease when infected with a second, related dengue strain. Similarly, dengue vaccination could also lead to enhanced disease, rather than protection, when a person subsequently encounters the virus. This additional safety concern has markedly complicated and slowed dengue vaccine development.
Zika causes mild fever in humans that on its own does not make a strong argument for a vaccine. But the possible link to microcephaly in unborn children, even though not yet definitely confirmed, makes vaccine development – and necessary funding – an urgent priority.
It’s also important to fund basic research to provide a necessary springboard for current and future vaccine development programs.
In the meantime, people in affected areas, including travellers, should take care to avoid mosquito bites by wearing long clothing and using repellents, bed nets and window screens.
Featured image: Flickr CC, Aedes aegypti, Marcos Freitas.