The emergence and spread of Zika virus across much of the globe led the World Health Organisation to declare a Public Health Emergency of International Concern in February 2016. It has been – and will be – crucial that the global response is informed by the best available research evidence and data. This is why, following the declaration, we joined leading global health bodies in committing to share data and results relevant to the Zika public health emergency and to future public health emergencies.
In November the WHO announced that the Zika virus outbreak was no longer a Public Health Emergency of International Concern. Nature Research will continue our commitment to free access in perpetuity to all papers submitted by the end of February 2017, regardless of the date they are actually published.
This blog looks back at some of the most significant Zika research published with Nature Research last year.
First experimental proof that Brazilian Zika virus causes birth defects in an animal model
This paper, published in Nature, reported that the Brazilian Zika virus strain can cross the placenta and cause growth restriction — including signs of microcephaly — in mice. These findings were the first experimental proof that Zika causes birth defects in an animal model. The paper also reported that Zika can infect human brain organoids in culture, inducing cell death and disrupting layers of neural tissue known as cortical layers.
These results reinforced existing evidence linking the Brazilian Zika virus outbreak to growing numbers of clinical cases of congenital malformations and may aid future pre-clinical studies, including vaccine development.
The first non-human primate model of Zika virus infection
For the first time, rhesus macaques were shown to be susceptible to infection by Zika virus, according to a study published in Nature Communications. The Zika virus strain used in the study, which is of Asian-lineage, was closely related to strains circulating in the Americas. The results implied that a new animal model of infection could be used to study Zika virus pathogenesis and to test potential therapies.
Moving towards a vaccine for Zika
A pair of related papers were published in Nature and Nature Immunology, describing cross-reactivity of antibodies to dengue virus with Zika virus. The former paper identified a region of Zika virus and dengue virus that was targeted by cross-reactive and neutralising antibodies to both viruses. The latter paper indicated that that the majority of dengue virus antibodies are unable to neutralize the Zika virus, and may enhance its replication. Taken together, these findings could further efforts to develop a vaccine that could potentially protect against both Zika and dengue.
Vaccine protection against Zika virus from Brazil
Single shots of either one of two types of vaccine can protect susceptible mice against the Brazilian Zika virus, reports a paper published online in Nature.
Researchers tested candidate vaccines in mouse models of Zika virus infection. They found that single immunizations with one of two types of vaccine — one made from DNA, the other a purified inactivated form of the virus — gave the mice complete protection against an isolate of the Zika virus from northeast Brazil. Although care should be taken extrapolating from this mouse study to potential human efficacy, the research raised hopes that a safe, effective human vaccine will become feasible.
1.65 million childbearing women at risk of Zika infection in the Americas
A model-based projection published in Nature Microbiology in July suggested more than 1.6 million childbearing women – and 93.4 million people in total – in the Americas could become infected during the 2016 Zika virus epidemic. The study suggested that, based on observed rates of adverse fetal outcomes in infected women, tens of thousands of pregnancies could be affected.
Drug screen identifies leads for Zika virus drug development
Compounds that suppress Zika virus replication or that prevent the death of cells infected by the virus were reported in a paper published online in Nature Medicine. These compounds — which include some drugs already approved to treat other human conditions — and their targets represent a starting point for anti-Zika drug development and preclinical studies.
Zika virus infection damages testes in mice
Male mice treated with antibodies to the IFN receptor to facilitate infection with a mouse-adapted strain of Zika virus can experience injury of the testes after virus infection, a Nature paper reported. The injury was associated with decreased testis size and reduced levels of two sex hormones and of sperm cells in the seminal fluid. The authors stressed that further work is needed to determine the extent to which these results in mice can be translated to humans.
Antibody treatment may protect unborn mice from Zika virus infection
A new antibody therapy that may prevent fetal damage in pregnant mice infected with the Zika virus was reported in a Nature paper. Owing to differences in gestational features between mice and humans, further studies are needed to determine whether the findings can be translated to the clinic, but it is hoped that the discovery will help to inform vaccine design efforts.