An affordable, oral vaccine against mosquito- and sexually-transmitted Zika virus

In February 2016 the WHO declared the Zika virus (ZIKV) to be a “Public Health Emergency of International Concern”. Experts now believe ZIKV is linked to a broad set of complications in pregnancy, including miscarriage, stillbirth, premature birth and eye problems with 29% of scans showing abnormalities in babies in the womb, including growth restrictions and microcephaly, in women infected with ZIKV. To clear viruses, the body generally requires both systemic and cellular immune responses, but unlike most insect-vectored diseases, ZIKV can also persist in semen and has been shown to spread as a sexually transmitted disease. That means mucosal transmission by travellers returning from any of the 43 endemic countries (population 525 million; 66 million tourists p.a.) may bring back and spread the disease in non-endemic countries. ZIKV has also been found in other bodily fluids including saliva and urine. Therefore, a vaccine that triggers systemic, cellular and mucosal immunity is needed, and preferably one that is easily manufactured and distributed under many different conditions. Prokarium’s oral vaccine platform, Vaxonella, mimics an intracellular pathogen and expresses vaccine antigens from within the immune cells of the gut lining. This means Vaxonella triggers all arms of immunity while reducing manufacturing costs by up to 70% due to the elimination of downstream purification of protein, which is always needed for injectable protein vaccines. In addition, Prokarium has developed a dried formulation of Vaxonella that is thermostable at 40 C for up to 12 weeks. These qualities are specifically suited to ZIKV and distribution to endemic areas as well as travellers, as Vaxonella vaccines can be produced almost anywhere and be self-administered. This temperature stability and self-administration will be useful in remote areas lacking medical personnel, but also for travellers if a booster is needed, as most travellers do not prepare ahead of time to take several doses of vaccine. Vaxonella is based on live strains of Salmonella bacteria that are weakened so that they cannot cause disease. The Salmonella are taken orally as a capsule (or as a liquid suspension for children); they transit the stomach into the small intestine where they actively enter through the gut lining into the antigen-presenting cells of the immune system (mimicking an intracellular pathogen). Using Prokarium’s proprietary genetic technologies, the Salmonella to be used in this project will be programmed to express protein antigens from ZIKV, and tested in mice to study the level of immune response generated. The best candidates will then be used to immunise mice which will be challenged with the actual ZIKV, using the existing subcutaneous challenge model at Public Health England (to mimick the mosquito bite route), who will also develop a novel vaginal challenge model (mimicking the sexually transmitted route), to see if they are protected compared to unvaccinated control mice. This will provide information to support further development of the ZIKV vaccine for future evaluation in human volunteers and represents the first known attempt to make a ZIKV vaccine that has a high chance of preventing both the insect-vectored and sexually transmitted versions of the disease.