Emerging Infectious Diseases
Along with the six Blueprint disease groups, the WHO has prioritised R&D preparedness for ‘Disease X’, which “represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease”. Funding for Disease X in this report includes the categories outlined below.
The categories for funding include fundamental research, vaccine platforms, adjuvants & immunomodulators, biologics- and drug-related platforms, general diagnostic platforms, and multi-disease vector control.
Fundamental research covers cross-cutting studies to increase understanding of multiple EIDs, which is not yet directed towards a specific technology. It includes research on disease surveillance and epidemiology, animal spill-over events, and pathogen biology. Viral surveillance studies in bats, for example, led to the 2018 discovery of Bombali virus, a new species of Ebolavirus. Pathogenesis studies using prototype viruses help define target antigens and develop assays; for example, understanding of molecular structures across the flavivirus family was instrumental in rapid translational research during the recent Zika outbreak.
Vaccine platforms include technologies and processes that allow the generation of immunogens applicable to multiple pathogens. Pre-existing safety and immunogenicity data and validated manufacturing practices allow rapid production and testing of platform-based vaccines. In 2020, a COVID-19 vaccine candidate based on an mRNA platform was identified in just 42 days – an industry record. Other technologies include viral vector- and nucleic acid-based (‘plug and play’) platforms. Self-amplifying mRNA (SAM) technology is being investigated in early-stage clinical trials for the development of second generation COVID-19 vaccines, while a pan-coronavirus vaccine technology based on the Ferritin platform has been developed and is entering Phase I clinical trials. The most advanced platform-based EID vaccine candidates include a prime/boost viral vector-based Ebola vaccine (Ad26.ZEBOV/MVA-BN-Filo) and several COVID-19 vaccines.
Adjuvants and immunomodulators are compounds or structures formulated to improve efficacy or duration of vaccine immunogens. Adjuvants play a key role in sub-unit or purified antigen-based vaccines, which lack immunostimulant properties. Current adjuvants have several drawbacks, such as inability to induce a cellular immune response. Adjuvants in development include MATRIX-M, which has been successfully combined with the R21 malaria vaccine candidate and is currently undergoing Phase III trials, and GLA-SE, a TLR4 agonist which has been combined with ID93 TB vaccine candidate in a successful Phase IIa trial.
Biologics- and drug-related platforms are adaptable technologies used for developing gene- and immune-based therapies. Current therapeutics platforms in development include DNA- and RNA-based monoclonal antibody (mAb) platforms and human polyclonal antibodies from transchromosomic bovine systems. This category also includes new delivery drug technologies and devices to simplify administration. Delivery technologies in development include nanoparticle-based drug delivery systems and controlled release formulation technologies such as PLGA micro- and nanoparticles, in situ gelling and liquid crystal formulations.
Broad-spectrum antivirals, which are also included here, are small molecule compounds which inhibit essential machinery of multiple virus families. The pipeline includes favipiravir, an RNA-dependent RNA polymerase inhibitor, UV-4B, an alpha-glucosidase inhibitor and nitazoxanide, an antiprotozoal agent recently investigated in late-stage clinical studies for use in treatment of COVID-19 and influenza.
General diagnostic platforms are rapidly adaptable tools for detecting pathogens for which commercial diagnostic tests are unavailable. During recent Ebola and Zika outbreaks, diagnostic platforms allowed rapid development of field-appropriate tests. Platform-based diagnostics include molecular (reference or point-of-care test), high-throughput testing based on real-time PCR and lateral flow rapid diagnostic assays. Diagnostic tests in development based on these technologies include real-time RT-PCR kits, RT-LAMP, antigen and antibody-based assays, and cartridge-based point-of-care molecular tests. Most recently, eRapid – a low-cost, affinity-based electrochemical sensing platform able to detect and quantify a broad range of viral biomarkers, has been developed and licensed for use in COVID-19 diagnosis.
The multi-disease vector control category captures funding targeting vectors capable of transmitting several different diseases. These include altering mosquito populations using genetic tools and sterile insect technique, chemical and genetic screens to identify molecules targeting Aedes aegypti mosquitoes, and Aedes-targeted Attractive Targeted Sugar Baits.