Source: Asia Development Bank
Decisions on vaccine platform choice should be context-specific.
Various vaccine technologies or platforms are available to help the body defend against pathogens (Table 1). While mRNA-based vaccines were the fastest to be developed and the most effective against SARS-CoV-2, the technology is not a solution for all pathogens. Each vaccine platform has its advantages and limitations, and choosing one depends on factors such as the pathogen, immune response, outbreak situation, cost, and ease of manufacturing.
The understanding of how the human body defends against different pathogens often guides vaccine technology selection. The two major protective, vaccine-induced immune components include: 1) neutralizing antibodies in the blood that can block infection and 2) immune T cells that kill infected cells. For example, the immune system combats bacterial infections through T-cell-dependent antibodies targeting the outer bacterial polysaccharide coating. As a result, most bacterial vaccines use polysaccharide conjugate vaccine technologies.
Tackling pandemic versus endemic pathogens requires vastly different vaccine development considerations. During a pandemic, rapid vaccine development technologies, such as mRNA, are critical. However, for vaccines against endemic pathogens, priorities may shift to long-term immunity and cost-effectiveness. When developing vaccines in or for populations in low-resource settings, cost and manufacturing complexity are key considerations. Furthermore, up-to-date knowledge of the major circulating pathogen strains—both locally and globally—and their associated epidemiology should inform vaccine development.
Investment in a range of vaccine platforms is critical for maximizing success.
As countries tackle a vast range of emerging infectious diseases, experts recommend judicious R&D investments in a variety of platforms, as well as innovations in manufacturing. The “portfolio approach” by the Coalition for Epidemic Preparedness Innovations (CEPI) is a case in point. It refers to the deliberate investment in a diverse range of vaccine platforms. Portfolio diversification enhances overall success by ensuring that different platforms do not share the same features and risks of failure.
Investment in early-stage R&D is instrumental for understanding how vaccine candidates provide protection and for generating evidence to support early go/no-go decisions in vaccine development. All vaccine R&D investments require a comprehensive assessment to evaluate market demand, barriers to access, and expected public health impact. For example, GAVI’s vaccine investment analysis framework aims to understand and capture the full value of vaccines, including social, economic, and population health benefits.
CEPI’s 100-day mission proposes to build a global vaccine library to promote coordinated investments and a global collaborative network for rapid content sharing. This initiative aims to build a library of vaccine prototypes and incorporate AI tools to forecast virus variants for high-priority diseases before their emergence.
Accelerating vaccine development requires multi-stakeholder effort.
The COVID-19 pandemic highlighted the possibility of drastically shrinking clinical development timelines by combining clinical trial phases and using adaptive trial designs. The use of immune correlates of protection (CoP)—i.e., immune parameters responsible for vaccine-induced protection—also enabled the rapid licensure of several COVID-19 vaccines. This was achieved through bridging studies, where immunology results from completed clinical trials were extrapolated to different populations. Fundamental research on high-priority pathogens is therefore crucial for establishing and validating CoP for future pandemic pathogens. Newer methods, such as controlled human challenge models, offer further potential to provide rapid insights into protection and safety.
Regulatory agility during the pandemic facilitated the expedited development of safe and high-quality vaccines. Similarly, regional and global collaboration in sharing manufacturing processes and vaccine safety and efficacy data further accelerated vaccine R&D. Therefore, continued data sharing, harmonization of regulatory requirements and resolving intellectual property issues will lead to faster availability of new vaccines during emergencies.
Limited infrastructure, funding, technical expertise, operational and manpower limitations currently hamper trials in resource-limited countries. Equitable vaccine access may be facilitated through international public-private partnerships in vaccine development and technology transfer. Understanding the magnitude and extent of knowledge and expertise gaps in these countries is important for guiding capacity building initiatives.
Affordability dictates the success of vaccine development programs in resource-limited countries.
Innovative strategies are essential in ensuring financial sustainability of vaccine R&D in lower-resourced countries. Design and discovery of new and improved vaccine technologies usually require decades of investment in basic scientific research, which is mostly sustainable in high-resource settings. To level the playing field, initiatives such as the WHO mRNA transfer hub and private and philanthropic joint ventures like Hilleman laboratories are working to make new vaccine technologies more accessible to lower-resource countries through technology transfer mechanisms.
Additionally, vaccine clinical trials require significant financial investments for setting up infrastructure, capacity development and clinical trial implementation. As a solution, WHO recently set up the Global Clinical Trials Forum to strengthen the clinical trial ecosystem in the Global South and promote domestic financing of clinical trials.
Table 1: Major Vaccine Platforms and Considerations for Development in Resource Constrained Settings