By Jerome Kim The International Vaccine Institute
Prior to the American entry into World War I, President Woodrow Wilson argued that the war should end with peace without victory. We often paint the current COVID-19 pandemic in the metaphors of war, and when we look at the end of the World War COVID-19 (C), do we see the “old normal” or a global landscape broken by suspicions, rancor and self-preservation?
While Wilson’s idealism did not survive the realpolitik of the moment, in this pandemic a vaccine is often considered the instrument of our return to normalcy. Assuming that a safe and effective COVID-19 vaccine does arrive in the next 6-18 months, will it bridge to a future that restores the status quo ante, or deepen, darken and inflame the worst that the current pandemic has nurtured? An effective vaccine(s) against COVID-19 holds great promise, but that promise will not be fully realized unless we think and prepare carefully for the future.
Beginning with the “End in Mind”
It is important that we have a clear goal in mind: a COVID-19 vaccine that enables a world without the disease or enough people vaccinated to create “herd immunity” so that individual cases of COVID-19 will not propagate through communities. Particular populations might be vaccinated first – health care workers, first responders, the elderly, people with risk factors. Gradually the vaccine would be offered to all, at a reasonable cost (or free), all over the world. Against those ideals, the reality of vaccine development provides grounding. The vaccine must be shown to work, to be safe and efficacious. The vaccine has to be made with high quality and in significant quantity (some multiple of 7 billion, assuming that everyone needs at least one dose). Finally the manufactured vaccine needs to be used, given to the 7 billion people who need it, achieving equity and access.
Proving that a Vaccine Works
Subject to urgency of the moment, the five to 10 years that it normally takes to develop a vaccine have been reduced to six to18 months. This process starts in a laboratory and then goes into animal testing, first for immune responses, then for initial safety – or “tox” – screening.
After a regulatory agency like the US Food and Drug Administration (FDA) reviews and accepts the paperwork documenting the creation, initial manufacturing, characterization, animal and future human studies, after ethical and scientific review, a vaccine enters Phase I testing in humans, usually a study of fewer than 50 volunteers, usually healthy adults, to ensure that no unexpected safety issues arise and to see if the vaccine induces the same protective (immune) responses in humans as in animals.
The data are often reviewed by an independent data and safety monitoring board, and a decision is made to proceed to Phase II of testing, usually involving several hundred volunteers, and really looking at protective immune responses (infection-fighting proteins called antibodies, “killer” T cells) in the target population (adults, infants, etc). The effect of different doses of vaccine or different vaccination schedules is evaluated at the same time.
If the vaccine induces the right immune responses, and the monitoring board finds no problems, the vaccine will advance into Phase III. Phase III trials are large and designed to show that the vaccine is safe and efficacious in preventing infection and/or disease. It is from the Phase III trial that scientists can say, “This vaccine reduces infection by 70 percent.” If a vaccine is safe and prevents infection, the company will present the paperwork on the vaccine trials in humans to the regulatory agency for their review and approval.
Making the Vaccine in Quantity with Quality
An approved vaccine also needs to be manufactured, and usually a company is preparing its manufacturing capacity while the vaccine is in Phase III of testing, so that the vaccine can be sold as soon as the regulatory agency gives approval.
Considering the accelerated timelines for COVID-19 vaccines, the early identification and engagement of companies that can quickly manufacture large quantities of vaccine at a quality sufficient to satisfy regulatory agencies is a critical path milestone for vaccine(s) entering Phase III testing.
For vaccines supplied to less developed countries, the World Health Organization (WHO) will do its own review and issue a “pre-qualification” letter that allows the vaccine to be purchased by United Nations agencies for organizations like Gavi, the Vaccine Alliance, which distributes vaccines at low or no cost to poorer countries.
Using the Vaccine and Ensuring Global Equity and Access
But even the availability of vaccines does not take us to the end in mind, since it is vaccination, and not vaccines, that protects people and societies. While the case for use of a COVID-19 vaccine may be obvious, usually a group like the Advisory Committee on Immunization Practices (ACIP) in the US or the WHO Strategic Advisory Group of Experts in Immunization (SAGE) will make a recommendation for vaccine use (after reviewing the data on safety and protection). The WHO recommendation is important because not all countries are comfortable deciding to use a vaccine that has financial implications against other national priorities in resource-limited settings.
The countries that have independently funded their own vaccine development, like the US and China, may be able to ensure that their citizens have priority when the vaccine first becomes available.
The Coalition for Epidemic Preparedness Innovations (CEPI) has received over a billion dollars from 13 countries, the European Commission, the Bill & Melinda Gates Foundation and the Wellcome Trust to develop vaccines against outbreak diseases, and COVID-19 is the pandemic that justifies CEPI’s creation.
CEPI’s funding of vaccine developers comes with a promise of global access, but the scale-up of vaccine manufacturing, the urgency of need, and the brutal logic of markets have serious potential to dwarf previous issues around the accessibility of masks and test kits.
So while vaccines are the most cost-effective weapons in the war against COVID-19, and our surest bridge “back to the future” of normalcy, we must take particular care in planning the development, manufacturing and roll-out of safe and effective vaccines against COVID-19.
Hopefully the anticipation of pressure points will allow us now, not when a vaccine first becomes available, to think through the medical, scientific and humanitarian issues that should warrant equity and access in the use of a COVID-19 vaccine.
As with the “War to End all Wars”, there will be no triumphal victor, but many victims, at the conclusion of World War C. Let’s hope the lessons of this struggle are not lost as we enter the post-COVID-19 future.
Jerome Kim is the director general of the Seoul-based International Vaccine Institute.
By Jerome Kim The International Vaccine Institute