Zika Virus Vaccine Programme
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 . 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.
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 . From then on, simian adenoviral vectors have been used to tackle multiple pathogens, such as rabies , HIV , P. falciparum and P. vivax malaria [4, 5], influenza , Rift Valley fever  and Ebola , 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.
1. Gulland, A., Zika virus is a global public health emergency, declares WHO. BMJ, 2016. 352: p. i657.
2. Xiang, Z., et al., Novel, chimpanzee serotype 68-based adenoviral vaccine carrier for induction of antibodies to a transgene product. J Virol, 2002. 76(6): p. 2667-75.
3. Clutton, G., et al., Transient IL-10 receptor blockade can enhance CD8(+) T cell responses to a simian adenovirus-vectored HIV-1 conserved region immunogen. Hum Vaccin Immunother, 2015. 11(4): p. 1030-5.
4. Ewer, K.J., et al., Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun, 2013. 4: p. 2836.
5. Reyes-Sandoval, A., et al., Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. Eur J Immunol, 2008. 38(3): p. 732-41.
6. Antrobus, R.D., et al., Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved Influenza A antigens. Mol Ther, 2014. 22(3): p. 668-74.
7. Warimwe, G.M., et al., Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice. Virol J, 2013. 10: p. 349.
8. Rampling, T., et al., A Monovalent Chimpanzee Adenovirus Ebola Vaccine - Preliminary Report. N Engl J Med, 2015.