Recombinant Outer Membrane Vesicles as a Novel Adjuvant for a Malaria Vaccine

Abstract While vaccines are an integral component of disease management, vaccine technologies remain inadequate for addressing malaria. Malaria caused by Plasmodium falciparum remains a global public health concern, with more than 229 million cases and 409,000 malaria-related deaths annually. The spread of drug-resistant parasites and insecticide-resistant mosquitoes has exacerbated the problem of controlling malaria in many developing countries in recent years. Current control measures such as bed nets, diagnostics, and drug treatment are helpful, however, together with more effective vaccines that reduce infection and transmission, cases of severe malaria may be eliminated. While an RTS,S virus-like particle vaccine targeting the sporozoite stage of P. falciparum is available, it remains only 30% protective in children that receive the vaccine, leaving children highly vulnerable. Versatope aims to address the unmet need for an effective malaria vaccine by leveraging their powerful, flexible, and thermostable vaccine adjuvant platform. The power of the technology platform is based on molecular engineering of recombinant outer membrane vesicles (rOMVs) derived from a probiotic E. coli Nissle 1917 strain (BSL-1) engineered with a lipopolysaccharide (LPS) and reduced endotoxicity. The resulting rOMVs are nano-sized particles that not only display foreign antigens of interest but also serve as potent adjuvants for long-term immunological memory and the induction of neutralizing and effector antibodies that protect against lethal pathogen challenge. rOMVs are stable under refrigerated conditions and can also be lyophilized and formulated for increased stability at room temperature, facilitating worldwide deployment. Using this platform, Versatope aims to deliver a malaria vaccine that acts as both a pre- erythrocytic and transmission blocking vaccine, protecting against both infection and transmission. The anticipated result of this Direct to Phase II proposal is selection and advancement of a malaria vaccine candidate that prevents liver-stage infection and reduces mosquito-borne-transmission. The success of Versatope’s malaria vaccine would represent a breakthrough in malaria reduction worldwide as an improved pre-erythrocytic vaccine(s) with substantially improved properties over the pre-erythrocytic RTS,S vaccine currently in use. Specifically, Versatope’s malaria vaccine would feature improved efficacy, longevity of immunity, reduced number of vaccinations, thermostability, and a lower cost of goods. The new pre-erythrocytic rOMV vaccine will target 70% efficacy in preventing new infections in infants and children. Together with a 70% reduction in infections provided by bed nets, this could reduce the R by a factor 10. The combined reduction in transmission of malaria provided by the pre-erythrocytic vaccine and current control measures (bed nets, access to health care, early diagnosis, and chemotherapeutic treatment) may not only allow global health programs to eliminate malaria from low transmission areas but may provide the potential for global eradication. This non-clinical development and toxicology program will advance the readiness of Versatope’s malaria vaccine for clinical evaluation and implementation in malaria endemic regions.