Clinical Development of a Zika Vaccine Avoiding Disease Enhancement

The Zika pandemic is a global problem with profound consequences for nations and families that will take decades to unfold, with an estimated 2.3 billion people at high or very high risk of infection (Alaniz AJ, 2017). However, Zika does not exist in isolation and is only one cog in a complex ecosystem of virus interactions where infection (or vaccination) of a human subject can give rise to antibodies that influence the course of other infections both positively and negatively. Zika is closely related to dengue (another virus infection, spread by the same mosquitoes), which is responsible for 390 million infections annually, and which is capable of causing life-threatening haemorrhagic fever. According to WHO, "An estimated 500 000 people with severe dengue require hospitalization each year, and about 2.5% of those affected die.". Recently, a new vaccine was licensed against dengue. While it is of net benefit to endemic populations (66% effective), on an individual basis it occasionally gives rise to severe dengue (the very disease it prevents in the majority of subjects) by generating antibodies that (paradoxically) enhance rather than prevent infection, requiring hospitalisation. Disease enhancement (eg. predisposition to severe dengue) is likewise a palpable risk for Zika vaccines in development, which may cause harm as well as good, depending on how a subject's immune system is conditioned by a Zika vaccine to respond to subsequent dengue infection or vaccination. Whether novel Zika vaccines succeed or fail may well depend on their capacity to avoid the generation of dengue-enhancing antibodies that have adverse consequences upon subsequent exposure to dengue. In the course of our recently completed Stage-I SBRI project 972224, starting genuinely from scratch, we made remarkable progress by developing and patenting a Zika vaccine candidate designed to avoid the generation of enhancing antibodies and predisposition to severe dengue. The Examiner has speedily approved all of the claims we made in the patent application (which was made under the Green Channel scheme). In the course of a second (diagnostic) SBRI project (971509, ongoing) we have explored several methods of production of the novel Zika vaccine antigen and have developed an efficient method ready to commence formally manufacturing development for vaccine use. Also, the 'pregnancy-test-like' point-of-cate diagnostic we have developed in 971509 can be deployed to identify suitable endemic locations for clinical trials (Phase-II) by allowing a very accurate and 'up-to-date' poll of Zika activity. In the present project we now propose to enter preclinical safety testing and early-stage (Phase-I) clinical studies - the latter to be sponsored by a partner company, spurred on by the advantages of our vaccine offering in concert with the strategic value of the diagnostic in enabling later-stage clinical trials.