Malaria killed about 640 thousand people in 2020, largely young children in Africa. Rapid recent progress has led to two anti-sporozoite vaccine developers planning WHO prequalification applications in 2022. These include the new high efficacy R21/Matrix-M vaccine, to be supplied at the required large scale, and led by partners in this consortium. In parallel, recent progress with transmission-blocking malaria vaccines has led to substantial efficacy in a first direct skin feeding field trial. This opens up the prospect of a two-stage vaccine targeting both sporozoites and sexual-stage parasites that should have a major impact on malaria transmission, thereby enabling regional elimination and ultimate eradication. We propose here to develop such a vaccine assessing both established virus-like particle (VLP) vaccines in potent saponin adjuvants and also exciting new thermostable mRNA vaccines expressing the parasite antigens now showing high efficacy. Importantly, we will adopt new VLP design technologies, e.g. SpyCatcher bonding, that allow bivalent antigen display, to enable a single vaccine to protect against both the Plasmodium falciparum parasite, which causes most deaths, and the more widespread Plasmodium vivax parasite. A lead vaccine candidate will be down-selected based on well-studied pre-clinical efficacy models and induction of functional transmission-blocking antibodies, prior to GMP manufacture and a clinical trial in year 4. The consortium brings together academics, non-profits and a wide range of companies with both leading technologies and access to small and very large scale GMP manufacturing capacity. This programme builds on the recent success of several partners in the R21/Matrix-M programme and aims to accelerate the malaria eradication agenda by providing the first vaccine to tackle both major malaria parasite species, and confer both individual and community protection on the way to eradication.

In the vaccine industry, downstream processing is of extreme importance. Prophylactic vaccines aim at protecting healthy people, so any contaminant has to be discarded with the most drastic measures. Such « negative » approach comes at the expense of the recovery of product : yields are poor, thereby inducing a high product cost. Processes are also complex, since they rely on multiple eliminations rather than on recovery of the unique product of interest. Technically, this is mostly due to the lack of specific capture systems that would allow direct, « positive » separation of the vaccine from its environment.Vaccines know no borders. For developing countries, the pressure on costs is even more acute, and local production is a way to try to reach the 1$ per dose target. In this context, water sustainability is a major issue, as it is a most sensitive ingredient in bioproduction. DiViNe will tackle theses cost and environmental issues with technological answers. The partners will combine two major Nano/biotechnology innovations to develop an integrated purification platform amenable to the different natures of vaccines : glycoconjugates, protein antigens and enveloped viruses. They will implement Nanofitins (novel affinity capture ligands) and Aquaporin-based membranes (energy-saving nano-biomimetics used in the cleantech industry), for a « positive » purification approach. High yields are expected (data from antibody purification with Nanofitins), at affordable cost of goods and with a sustainable approach of water recycling. Novartis Vaccines brings to the Consortium a broad range of targets, and identical strategies can be applied for biopharmaceuticals in general. The development custom affinity capture processes as a sustainable platform is therefore economically relevant, in a very large market. Beyond the technical partnership, the project is a first run for the partners to structure the platform as a commercial offer for downstream processing of biologics.