The CARES Act requires the Government Accountability Office (GAO) to look at the government’s response to the COVID-19 pandemic, including vaccine development.
The government watchdog has found that, overall, vaccine development is still difficult, complex, and costly. However, in a November 16 report, it identifies numerous innovative technologies and approaches that may enhance the nation’s ability to respond to high-priority infectious diseases.
Technologies and approaches for vaccine research and development:
Omics refers to the combined analyses of DNA (genomics and epigenomics), RNA (transcriptomics), proteins (proteomics), other small molecules (metabolomics), and other biological components. In vaccine R&D, omics is meant to improve the understanding of pathogens and host immune responses.
Reverse vaccinology uses computer-based analytics to assess a pathogen’s genetic code and identify potential antigens. Reverse vaccinology allows researchers to identify potential vaccine antigen candidates without the need to grow the pathogens and develop vaccines that were previously difficult or impossible to make.
Next-generation vaccine platforms
Next-generation vaccine platforms incorporate the genetic information that codes for a pathogen’s antigen into a delivery vehicle. A delivery vehicle can be another virus (viral vector), a microparticle, or a lipid nanoparticle. The delivery vehicle protects the genetic information until it is administered into an individual, where the immune response is triggered. The platform may also be able to be used in a plug-and-play fashion to pair a delivery vehicle with different genetic sequences to create new or updated vaccines. Vaccine platforms may have uniform, predictable characteristics, such as safety effects; however, each antigen in a specific platform will have different immune response characteristics.
Routes of vaccination
Traditional vaccinations are delivered by injection either under the skin (subcutaneous) or into muscle (intramuscular). The identification and use of nontraditional vaccine delivery routes, such as dermal (skin) and mucosal (oral, nasal) may offer the potential for better immune responses, increased public acceptance, and lower dosages.
Technologies and approaches for vaccine testing:
Populated with cells and used in preclinical studies, organ chips mimic the function of human organs and can be used to study the effect of a vaccine candidate.
Artificial intelligence (AI) and machine learning (ML)
AI and ML systems can analyze large amounts of data gathered during preclinical studies and clinical trials.
Electronic health records (EHR)
An EHR is a digital record of a patient’s medical information that can be used to support trials for patient recruitment, clinical data analysis, and post-trial followup.
Common control groups
A common control group allows multiple groups of participants in preclinical studies or clinical trials to be compared with a single control group, reducing the number of participants needed or enabling comparison among vaccine candidates.
Standardized assays are standardized tests or investigative procedures that can potentially be used by different vaccine developers to determine the immune response induced by a vaccine candidate. For example, standardized assays could measure the presence of antibodies in clinical trial participants who have received different vaccines candidates.
Virtual clinical trials and wearable devices
Virtual clinical trials, also referred to as decentralized trials, extend the reach of clinical investigations to where patients live and work. Data for virtual trials can be collected remotely via wearable digital health technologies including watches, bracelets, patches, textiles, and clothing.
Technologies and approaches for vaccine manufacturing:
Single-use systems refer to bioprocessing equipment that is designed to be used once and then discarded. Such equipment is generally composed of sealed, pre-sterilized, plastic components.
Modular bioprocessing systems
These systems divide the manufacturing process into smaller functional building blocks known as modules, suites, or pods that can stand alone or be incorporated into an existing facility. For example, new modules can be added to quickly expand capacity or switched to rapidly change processes, according to an expert GAO spoke to.
Biological enzymes—proteins that cause biochemical reactions—are used to generate antigens, which are then combined with other materials to create vaccines.
This approach improves the cells and growth ingredients—known as medium—and other processing steps. According to an expert GAO interviewed, this technology may increase productivity and allow manufactures to get more out of the same equipment or facility.
Continuous manufacturing systems
These systems use automated, high-throughput, small-footprint production and purification equipment to manufacture vaccines. In contrast to existing batch processing methods, which use separate tanks for each step in the process, continuous manufacturing allows all steps of vaccine production to continue without interruption as the materials flow through the system.
GAO also found key challenges that may hinder the adoption of these innovative technologies and approaches, such as inherent technical limitations and high cost. For example, organ chips may facilitate testing, but they are not yet able to replicate many of the complex functions of the human immune system. Similarly, single-use systems may increase the flexibility of vaccine manufacturing facilities, but may require extensive testing to ensure that they do not negatively affect the resulting vaccine. Further, economic challenges may hinder vaccine development. Experts attribute underinvestment in vaccines to market failures (i.e. market interactions that fall short of what would have been socially beneficial). For example, vaccines benefit those who are vaccinated, and, to some degree, those who are not. This additional benefit is not captured in the price, which reduces return on vaccine investment.
As part of its review, GAO identified nine policy options that may help address challenges hindering the adoption of vaccine development technologies and approaches or economic challenges. These policy options involve possible new actions by policymakers, who may include Congress, federal agencies, state and local governments, academic and research institutions, and industry.
For example, policymakers could collaborate across sectors (e.g., government, academia, researchers, industry, and nonprofit organizations) to prioritize infectious disease pathogens with pandemic potential for vaccine R&D. In addition, GAO says policymakers could provide support for public/private partnerships to strategically develop manufacturing capacity to respond to surge requirements. To maintain this capacity, partnerships could manufacture prototype vaccine candidates against high-priority pathogens. Further, the watchdog would like to see policymakers collaborate across sectors, such as government, academia, and industry, to conduct a systematic evaluation of factors that inhibit developers from investing in new vaccines.