This post was originally published on the website of the Foundation for Biomedical Research (FBR) January 28, 2016. It is republished here with permission from FBR.
The major public health problem of 2016 has been the sharp rise in the ongoing outbreak of the Zika virus, as well as its probable link to microcephaly in infants. While Zika has been on the rise since 2014, it has recently reached pandemic levels and is forecast to spread to nearly all of North America; outbreaks in southern Europe are also possible. There is no vaccine or treatment for the virus, which is spread through mosquito bites. It causes an illness similar to a mild form of dengue fever, but the biggest threat from the virus is the link to Guillain–Barré syndrome in some patients and microcephaly when pregnant women are infected.
As public health officers worldwide scramble to understand and control the explosive spread of the disease and its threat to pregnant women and their unborn children, animal research will play a pivotal role. Francis Collins, director of the National Institutes of Health has said, “It is now critically important to confirm, through careful epidemiological and animal studies, whether or not a causal link exists between Zika virus infections in pregnant women and microcephaly in their newborn babies.” Animal research will be integral in the discovery of vaccines and treatments to stop the spread of Zika.
Even before effective treatments are found, animal research is helping in the fight against Zika. The CDC recently directed healthcare providers to screen pregnant women who have travelled to areas affected by the ongoing Zika outbreak for the presence of the virus. Doctors will perform the blood-based tests using reverse transcriptase-polymerase chain reaction (RT-PCR) on serum. RT-PCR testing has its origins in animal research: as early as 1908, Danish scientists working with chickens produced results that laid the foundation for Howard Temin’s 1970 discovery of the reverse transcriptase enzyme, which is the heart of RT-PCR.
With a treatment still in the future, public health officials have focused their efforts in slowing the spread of the virus. Speaking on ‘CBS This Morning’, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases shared details of his recent meeting with President Obama; “What we spoke to President Obama about… was the kind of countermeasures – better diagnostics, the development of vaccines, being able to understand the virus better, vector control… that he was very interested in.”
Scientists and physicians at the U.S. National Institute of Allergy and Infectious Diseases (NIAIAD) issued a notice highlighting their intention to fast-track funding for Zika research. One of their central aims is the development of animal models to study the disease and test potential treatments. The notice calls for “Studies to develop animal models to study ZIKV pathogenesis (especially neurological manifestations and teratogenic potential) and evaluate candidate therapeutics and vaccines.”
To fight against the transmission of Zika, Dengue and Chikungunya, the Pasteur Institute is trying to genetically modify mosquitoes so they are unable to transmit the virus. Moreover, “teams are already developing animal models within the institute” to explore the connection between Zika virus and birth defects, according to the specialist Anna-Bella Failloux. Together with the Instituto Oswaldo Cruz in Rio de Janeiro (Brazil), researchers from the Pasteur Arboviruses and Insect Vectors Unit have tested the susceptibility (the ability to contract the virus) of Aedes aegypti and Aedes albopictus mosquitoes from Brazil and Florida, where these two species co-exist. In addition, they have assessed the ability to transmit the virus in Aedes aegypti in French Guiana, Martinique and Guadeloupe, where this is the only species present.
These populations of mosquitoes, recently collected in the field, were infected in a BSL3 laboratory with the Asian genotype Zika virus from the Institut Pasteur in New Caledonia. This virus is almost identical to the one currently circulating in Central and South America. The aim of this current research is to establish the role of the Aedes aegypti and Aedes albopictus species in the dynamics of the Zika epidemic in the Americas. This data will be used to assess the potential scope of the epidemic and determine whether it could reach the scale of the chikungunya epidemic. If Zika proves to be a long-term problem, researchers may utilize gene editing to create mosquitoes resistant to the virus. Similar efforts are currently underway in the fight against malaria.
Once scientists understand enough about the Zika virus to begin developing a vaccine, animal research will be the foundation of vaccine development. Having identified antigens that could provoke beneficial immune responses to the virus, researchers conduct pre-clinical testing. Cell-cultures and animal models – most often mice and primates – are tested for response to the antigens. Researchers may also conduct ‘challenge studies’, vaccinating an animal then attempting to infect it with the virus. Such research is crucial for determining the effectiveness and safety of potential vaccines and the potential cellular response in humans. Only the best candidate vaccines make it through pre-clinical animal testing.
At every phase of response to the Zika virus – diagnostics, understanding the virus, vector control and the development of vaccines – animal research provides an indispensable resource for researchers. Research in animals provided the pre-existing tools, such as RT-PCR testing, and will be a central component of new efforts – from developing therapeutics and vaccines to tackling the vectors that enable the virus to spread. The rapid rise of the Zika virus and worldwide response highlights just how essential animal models are in modern public health.