Innovative technologies for the production of groundbreaking biopharmaceutical products in microbes and plants

Malaria still affects more than two million people and is responsible for over 600,000 deaths each year, primarily in developing countries. The complex, multi-stage life cycle of the parasite Plasmodium falciparum makes vaccine development challenging but also provides a wide range of potential vaccine targets. Within this project, we are working on the development of novel multi-stage, multi-component malaria vaccine cocktails produced in plants. We have identified a potent antigen combination that shows promising inhibitory potential against all stages of Plasmodium falciparum. To evaluate this new malaria vaccine candidate in initial clinical trials, the candidates will undergo accelerated GMP process development so that they can be produced in the fully automated, process-controlled vertical farming unit currently under construction at Fraunhofer IME in Aachen.

Malaria remains a major burden on healthcare systems and economic development in many developing countries, especially in sub-Saharan Africa. Traditional control strategies—such as insecticides and mosquito nets to prevent transmission, combined with the use of artemisinin-based combination therapies to treat infections—have significantly reduced disease incidence and increased hope for malaria eradication in the future. However, the continuous emergence of drug resistance in both the mosquito vector and the parasite complicates this goal. Therefore, the availability of a vaccine capable of preventing infection, the manifestation of clinical symptoms, and disease transmission represents the most promising strategy. Although numerous vaccine candidates have been evaluated in clinical trials over the past decades, none have demonstrated sufficient efficacy.

Most malaria vaccines tested so far target only one of the three main stages of the P. falciparum life cycle. Vaccines aimed at the pre-erythrocytic stage are designed to provide complete protection by preventing the parasite’s initial invasion of liver cells following a mosquito bite. Approaches that specifically target blood-stage antigens have the potential to stop or reduce parasite replication in the bloodstream, thereby preventing the manifestation of clinical malaria. So-called transmission-blocking vaccines target the sexual stages of P. falciparum and aim to reduce the spread of the disease within a population.

Given the limited success of single-component or single-stage malaria vaccine candidates, novel combinations of antigens are now considered a promising strategy to finally identify an effective malaria vaccine.

In an iterative process, we used our powerful transient plant expression platform to produce a large number of P. falciparum antigens or antigen fusions derived from the three main life cycle stages and evaluated their vaccine potential in immunization studies followed by specific in vitro efficacy assays. Through this strategy, we identified an antigen combination that, when tested as a multi-stage, multi-component vaccine in rabbits, achieved an 80% inhibition of pre-erythrocytic parasite stages, a 90% reduction of red blood cell invasion, and up to a 95% inhibition of late sexual-stage parasites.

To evaluate this promising vaccine cocktail in initial clinical studies, an accelerated GMP process development was initiated. Production was carried out in a fully automated and process-controlled vertical farming unit at the Fraunhofer IME in Aachen.