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A new Zika vaccine based on a simian adenoviral vector is being developed in Oxford to determine if it is immunogenic and can be taken to clinical trials. This development is part of a global rapid response programme. 

Zika vaccine programme 

On the 1st of February 2016, the World Health Organization (WHO) declared the Zika virus an international public health emergency due to its link to congenital malformations and neurological complications.

The major concern by WHO has been the association with microcephaly, a condition that causes babies to be born with abnormally small heads, an indication that the brain has failed to develop properly. The move has triggered funding into research, vector control and efforts to prevent pregnant women becoming infected [1]. The group lead by Prof. Arturo Reyes-Sandoval has initiated a programme to develop a Zika vaccine, with  Dr. Cesar Lopez-Camacho, a postdoctoral scientist at the Jenner Institute. 

Research aims 

This Zika vaccine uses a non-replicating simian adenoviral vector expressing the structural antigens of the Zika virus, with the aim of inducing strong humoral and cellular immune responses with no requirement for an adjuvant. Vaccines using this type of simian adenoviral platform were initiated by Prof. Hildegund Ertl at the Wistar Institute in Philadelphia, where Reyes-Sandoval was part of this pioneering group back in 2002 when the use of these sub-unit type vaccines was first reported [2]. From then on, simian adenoviral vectors have been used to tackle multiple pathogens, such as rabies [2], HIV [3], P. falciparum and P. vivax malaria [4, 5], influenza [6], Rift Valley fever [7] and Ebola [8], amongst others. 

Simian adenoviral vectors are preferred over human adenoviruses because they do not circulate in our population and immunity against the vaccine platform (anti-vector immunity) is weak. Thus, the vaccine retains its capacity to induce robust immune responses. In addition, these platforms are considered to be safe because they do not replicate inside the human body after injection, since genes required for replication are replaced by the Zika virus structural proteins. Complexity is reduced even more because the adenoviral vectors do not require adjuvants to stimulate strong immune responses. Viral vectors provide ‘danger’ signals recognised by the body’s immune system to prime both arms of the adaptive immune responses: antibodies and cytotoxic T cells. This creates an advantage over other vaccines made using proteins or virus-like particles (VLPs), which require adjuvants that in many circumstances are difficult to obtain. 

Simian adenoviruses have great plasticity allowing use for many diseases. Genetic sequences of interest can be cloned into the virus and are expressed once a person receives the vaccine. The innate and adaptive (antibodies and cytotoxic T cells) arms of the immune system react against the virus and the Zika antigens to create immunological memory that can protect against infection when an individual is subsequently exposed to the Zika virus itself.

Arturo Reyes-Sandoval’s team is expected to have a Zika vaccine ready for pre-clinical tests by April 2016 and if funds are available, the vaccine will be tested in clinical trials by 2017. 

Selected publications