The Task Force’s Brighton Collaboration is a group of more than 750 vaccine experts working on vaccine safety who are monitoring and informing the development of COVID-19 vaccines. The Task Force’s vaccine safety expert and Brighton’s Scientific Director, Robert “Bob” T. Chen, MD has been a leader in research on the epidemiology of vaccines and vaccine-preventable diseases at the Centers for Disease Control and Prevention for more than 30 years. He helped create the vaccine safety infrastructure needed to meet the “post-modern” challenges of mature immunization programs. Chen shares the basics of vaccine development for COVID-19.
1. Vaccine developers have been working on a COVID-19 vaccine since the beginning of this outbreak. What is the current status of a potential vaccine?
Until the trials that are underway reach completion, we can’t make a valid prediction about when a vaccine could be ready for distribution. However, there are three potential vaccines in phase one of clinical trials in which small groups of people receive the vaccine candidate. And more promising yet, there are five vaccine candidates in phase two of clinical trials in which a larger group of people with representative characteristics of the target population receive the vaccine candidate. Unfortunately, timing for each phase and each trial is different so it is hard to predict when results will be available from these various trial vaccines.
The information on these trials is changing rapidly and reliable sources like Scientific American are a good way to stay informed about the development of a COVID-19 vaccines.
2. What is the process for testing and approving a new vaccine and what procedures help ensure that it is a safe vaccine?
While we ourselves are not developing new vaccines, we do help advise the development process which includes six stages outlined by the Centers for Disease Control and Prevention. These stages include 1.) the exploratory stage, 2.) pre-clinical stage, 3.) clinical development (which includes phases 1-3), 4.) regulatory review and approval, 5.) manufacturing and 6.) quality control. As I mentioned, there are eight vaccine candidates in various phases of the clinical development stage right now. Besides those, there are 132 candidates in the pre-clinical stage of development.
In the U.S., new vaccines that a developer wants to test must first be accepted by the U.S. Food and Drug Administration (FDA) through an application process that describes the vaccine, its method of manufacture, quality control tests with information about the vaccine’s safety and ability to elicit a protective immune response (immunogenicity) in animal testing, and the proposed clinical protocol for studies in humans.
Measures for creating a safe vaccine are implemented and evaluated at all stages of the process and continued even after the process is completed and vaccines are distributed.
3. How is The Task Force’s Brighton Collaboration providing vaccine safety expertise and guidance to vaccine developers?
At the beginning of the outbreak, one of the concerns was whether a vaccine against this coronavirus may actually create a “bad” type of immunity so that subsequent reinfection by coronavirus in a person previously vaccinated would result in a worse COVID-19 disease. This “vaccine-mediated enhanced disease” phenomenon was observed with earlier animal studies of vaccines against other types of coronaviruses. The Task Force’s Brighton Collaboration, in partnership with the Coalition for Epidemic Preparedness Innovation (CEPI), quickly convened a virtual meeting of global experts to reach consensus on how to assess disease enhancement for all COVID-19 vaccine candidates at various stages: pre-clinically, during clinical trials and after vaccine approval.
Also, through the CEPI-funded Safety Platform for Emergency vACcines (SPEAC) Project, we have drafted lists of potential adverse events of special interest for COVID-19 vaccine candidates which are reviewed by the World Health Organization. Adverse events are poor reactions in a human’s body when they take a medicine or treatment, and vaccine developers include these lists of potential adverse events in their protocols for vaccine trials so that they can effectively monitor them if one should occur. Similarly, various national monitoring systems for adverse events following immunizations can utilize these lists to prepare for mass vaccination campaigns. Building on Brighton Collaboration’s tradition in developing standard case definitions, we are also creating disease case definitions for several COVID-19 adverse events.
4. How are trials being conducted to ensure safety of candidates while also meeting the urgent need for a vaccine?
It requires careful balancing of many scientific and non-scientific issues. The Brighton Collaboration focuses on a variety of these issues to ensure the scientific data on safety is as good as possible. This is very challenging because generally the safety of a vaccine cannot be directly measured; we can only infer whether a vaccine is safe by assessing the absence of adverse events during testing. From these findings, we create the vaccine’s “safety profile.” Vaccine development companies and country-specific regulatory drug agencies like the FDA work together to define how long a vaccine is tested among how large of a population to generate the data for the safety profiles.
For a COVID-19 vaccine, the Collaboration is creating standard disease case definitions for adverse events. These standard definitions are the foundation of developing a safe vaccine because they act as a sort of Rosetta Stone for all vaccine developers, allowing stakeholders to accurately count and compare adverse events and therefore safety profiles across vaccine trials. As the trials progress, we’re formulating additional case definitions that are needed for COVID-19 vaccines, improving them as we learn more about the disease.
Vaccine developers are also using a variety of technology platforms to create potential COVID-19 vaccines. Some platforms like mRNA- or DNA-based vaccines – vaccines that use genetic coding to increase the production of antibodies – have never been licensed in humans before. To help stakeholders, we have developed reporting templates for each of these various technology platforms so that vaccine developers can clearly communicate the features of their vaccine candidate to regulatory agencies, other researchers, etc. The features often involve highly complicated biotechnological language which can delay the approval process, so these templates will allow approvers to quickly assess a vaccine candidate while ensuring that it meets all the necessary safety requirements.
These types of tools and resources help vaccine developers and approval agencies create and approve the safest vaccine even in a time-crunch. They are also beneficial resources to vaccine recipients, scientists, health officials and healthcare providers, who need to obtain, interpret, provide, and report information on immunization safety to make scientifically sound decisions.
