In 2015–2016, the Zika virus ravaged South America, with major effects on pregnant women and their unborn children because the virus can harm the fetus. Researchers have difficulty in studying Zika in classical animal models because mice are less receptive to Zika virus infection than humans. Danish researchers have now found a new way to solve this problem and are making advances in developing a vaccine. The race is now on to achieve results before the next outbreak occurs in a new location.
Pregnant women need to be careful when travelling to mosquito-infested countries in Africa and Asia and, since 2015, South and Middle America and now Florida and Texas in the United States. The Zika virus is mainly transmitted through mosquito bites, and although most adults do not develop any symptoms, in pregnant women the infection can lead to the underdevelopment of the fetal brain and head. There is now important news on the effort to develop a vaccine before the next Zika wave breaks.
“The big problem is when Zika strikes a new region, which is what happened in 2015–2016 when Zika rapidly swept through the population of 30 South American countries. Our new results suggest that people who were infected develop solid protective immunity by developing antibodies against Zika. This means that we hopefully can call off the most catastrophic scenarios, and we now know how to develop a vaccine and can take all necessary steps to achieve this before the Zika virus strikes again – in a new place,” explains a main author, Loulieta Nazerai, PhD student, Department of Immunology and Microbiology, University of Copenhagen.
First massive wave of attacks
The Zika virus is scarcely new. It has been known from Africa and Asia since 1947 – without making the headlines. This finally happened in 2007, when the first major outbreak occurred in Micronesia. However, the 2015 outbreak in Brazil was the most widely reported one. The coverage showed gruesome pictures of babies with small heads and brain damage. In addition, some adults may develop Guillain-Barré syndrome, which is a disease affecting the peripheral nervous system and associated with limb paralysis. The researchers’ current theory is that a single traveller – probably from French Polynesia – transmitted the virus.
“The Zika virus moved to a completely new region in which nobody was immune to Zika. Most of the population became infected very quickly, and many pregnant women and their fetuses were therefore affected. Now, a few years later, most of the population seems to have become immune, which is why we do not expect an equivalent outbreak in these regions again.”
The basis for a population developing immunity seems to be that the infection leads to a long-lasting antibody response and memory cells that react to the virus.
“This means that a massive problem only arises during the first wave of an attack. It also means that we can draw on previous experience to produce the type of vaccine necessary to immunize the rest of the population. Although much work remains to be done to develop the specific vaccine, we now basically know what we need to do, so it should only be a question of time before a vaccine is developed.”
Transmitted also through sperm
One reason for the delay in producing a vaccine is the difference between people and mice. In humans, the Zika virus inhibits the production of type I interferons, an important regulator of the immune system. This enables the virus to establish itself more or less freely. When researchers tried to study this in mice, they were in for a surprise.
“The Zika virus does not inhibit the production of type I interferons in mice. If, as a result of this knowledge, research were conducted on mice that do not produce type I interferons, other functions of the immune system would also be affected that would create difficulty in identifying the immune components that protect against the infection. Luckily, we had previously worked on yellow fever, which is also caused by a flavivirus closely related to Zika. With yellow fever, we had found out that we could actively infect the mice by injecting the virus directly into the brain. Using this technique, we could use mice to discover how activating the immune system could protect against disease,“ explains another main author, Allan Randrup Thomsen, Professor, Department of Immunology and Microbiology, University of Copenhagen.
Although the World Health Organization has toned down its initial catastrophic warnings on the global threat of the Zika virus, a vaccine is still sorely needed. The virus is spreading increasingly northward in the United States, and with a warming global climate, the mosquito and its attendant viral diseases are expected to move further north. This provides Zika with opportunities to ravage new areas.
“Developing a vaccine is necessary both for regions we expect will be struck in the near future and also for the parts of the population in the affected regions that are not yet infected. Developing a vaccination programme that will enable the whole population to become fully immune would make sense, such as with rubella in Denmark.”
Danes are keen travellers and although they live in northern latitudes they should not feel completely safe because the Zika virus is unfortunately transmitted in other ways than by mosquitoes.
“A man who travels to an affected region and is infected with the Zika virus risks transmitting the infection to his partner through his sperm. The virus has been detected in sperm up to 2 months after an infected man has had symptoms, so developing a vaccine is also very important for people travelling to these regions.”
“A New In Vivo Model to Study Protective Immunity to Zika Virus Infection in Mice with Intact Type I Interferon Signaling” has been published in Frontiers of Immunology. The Lundbeck Foundation is the main donor to the project, headed by Jan Pravsgaard Christensen, Søren Buus, Anette Stryhn and Allan Randrup Thomsen. The Novo Nordisk Foundation awarded a grant in 2010–2016 to Allan Randrup Thomsen, Department of Immunology and Microbiology, University of Copenhagen for research on the role of type I interferon and aspects of virus-induced inflammation and other topics.