Abstract
Vaccines are the cornerstone of the management of an infectious disease outbreak and are the surest means to defuse pandemic and epidemic risk. The faster a vaccine can be deployed, the faster an outbreak can be extinguished. To date, however, the pharmaceutical response to emerging infectious diseases and bioterrorism has been characterized by a “one bug, one drug” approach, in which specific medical countermeasures—effective vaccines and therapeutics—are developed, manufactured, and deployed. This is a process that is often measured in decades.
However, over the past several years, platform technologies have been developed that could make it possible for multiple vaccines to be more rapidly produced from a single system. In fact, the 2 vaccines being deployed in the Ebola outbreak in the Democratic Republic of Congo are both platform-based.
In 2018-19, the Johns Hopkins Center for Health Security conducted a project to elucidate the promise and challenges of vaccine platform technologies. The overarching aim of the project was to develop a state-of-the-art conceptual understanding of various vaccine platform technologies, with special attention to how they might speed development of vaccines for global catastrophic biologic risks (GCBRs) and emerging infectious disease outbreaks. The report describes major scientific and policy issues related to platforms and how they are understood in government, academia, and industry, and it provides recommendations aimed at helping realize the potential benefits of vaccine platform technologies.
What follows is a brief summary of the most salient issues identified in the report that are important as platform technologies proliferate and are increasingly favored as a means for vaccine development. Recommendations for how to capture the full value of platform vaccine technologies were also made and are included in this commentary.
Definitions Vary
Among the various vaccines that currently exist or are in development, the criterion that classifies each vaccine candidate as a “platform”—or not—is unclear. For our project, a technology was defined as a platform if an underlying, nearly identical mechanism, device, delivery vector, or cell line was employed for multiple target vaccines. Platforms have the potential to lead to the development of multiple vaccines, with 1 substratum-like component being amenable to the development of multiple disparate vaccines; they are pluripotent.
There is a clear cachet, from an investor or public relations standpoint, in being labeled a platform, irrespective of whether the underlying process is truly platform based. As long as objective definitions and conceptual clarity are lacking, analyzing the promise and needed policy and science around platforms will be challenging. A sharper understanding of what constitutes a “platform” technology is needed.
A Spectrum
There exists a spectrum of attributes possessed by certain vaccine technologies that render a vaccine more or less platform based. The process by which a vaccine is manufactured qualifies it as platform based. If it has the capacity to form the basis of myriad other vaccines using some conserved structure, it can be classified as a platform. The spectrum of different platforms ranges from viral vectored vaccines to nucleic acid vaccines. Thinking of platforms as being situated on a spectrum helps to minimize definitional disputes, as there are different variations of platforms. Overly restrictive definitions—such as limiting platforms to viral-vectored vaccines—could become obstacles to research and development.
Products Licensed, Not Platforms
Despite the potential manufacturing flexibility that platforms offer, regulatory agencies approve products, not platforms. Such agencies evaluate submissions as whole products intended for human use rather than as components. Each product submission, irrespective of its relationship to an existing platform, is viewed as a whole. But with increased use of a specific technology, regulatory agencies may, over time, become more comfortable with how such a technology works and the overall safety and efficacy profiles of the products produced, allowing more rapid approval and less onerous approval decisions with each subsequent submission.
Diminishing Rate-Limiting Elements
Much of the current discussion on the benefits of platforms centers disproportionately on hope that the regulatory process will be streamlined, but there is no plan for such a streamlining at this time. However, even without any new, special regulatory considerations being given to platform-based vaccines, the speed of the general platform-based approach—even if restricted to the pre-investigational new drug (pre-IND) phase—will likely have a significant, measurable impact on vaccine availability.
Lowering the Risk
Because a platform vaccine technology can be leveraged for multiple uses—both for emerging as well as routine infectious diseases—a platform can be a means of achieving economies of scale and lowering the risk of ventures in emerging infectious diseases. Platform vaccine technologies are a sustainable pluripotent infrastructure that can be applied to emerging infectious disease vaccines with minimal added financial risk, thereby diminishing costs of vaccine development.
Recommendations
Whether a vaccine is designated “platform-based” should not be a factor in the speed with which it is developed. Increasing the availability of vaccines (platform- and non-platform-based) should be the overarching policy goal. Because of the enhanced awareness, value, and funding opportunities related to the ability to describe a vaccine as platform based, companies may divert resources to making the case that their vaccine meets the criteria to be called a platform. By conceptualizing platforms as falling on a spectrum, and recognizing that more than one variety of platform technology exists, this type of strategic positioning may be minimized.
The anticipated development speed of platform-based vaccines should not assume that regulatory streamlining will occur. The rapidity of development using platforms may largely be the result of the relative ease in reaching pre-investigational new drug (pre-IND) stages of development and may be very consequential, even with standard regulatory timelines post-IND.
The traditional approach to vaccine R&D should not be entirely supplanted by platform approaches. While platform-based approaches might be the future of vaccine development for many targets, there are infectious disease targets that currently exist or will likely emerge for which a traditional vaccinology approach might be most likely to succeed.
An mRNA-based vaccine platform technique appears particularly promising in terms of ease of manufacture, adaptability to various targets, and biological delivery.
Platform vaccine technologies, like all other emerging infectious disease medical countermeasures, require special considerations, given market conditions. Despite the economies of scale achievable via platform-based approaches, emerging infectious diseases, by their very nature, will never represent a major market with large financial rewards and minimal opportunity costs. Dedicated programs by governments, nongovernment organizations, and philanthropies will likely play major roles for the foreseeable future in the development, uptake, and use of vaccine platform technologies.