How much longer do we need to wear these masks?" might be voted the question most often asked of fire and EMS chiefs. Many of our imaginations see the arrival of a COVID-19 vaccine signaling a swift return to our normal, pre-COVID lives. In reality, chances are quite slim that this novel coronavirus, which moderately understood at best, will come to an abrupt end as a result of a vaccine, treatment, or even a mutation in the virus itself.
Understanding the vaccine development process, implications for public safety, past efforts to eradicate disease with vaccines, and typical timelines is essential for fire service leadership planning and education.
Vaccines prevent two to three million deaths annually1, so there is little wonder why over 130 COVID-19 vaccines are currently in development. Vaccines2 halted terrible diseases like smallpox, diphtheria, tetanus, measles, and meningitis that wiped out large portions of the world population.
False information disseminated by anti-vaccine movements has led to many of these diseases' resurgences and rapidly increasing preventable deaths worldwide3. Hesitancy induced by anti-vaccine campaigns will likely undermine COVID-19 vaccination, once available. Development efforts continue on vaccines for AIDS, tuberculosis, malaria, cancer, and Alzheimer's. While Ervebo, the Ebola vaccine approved in 2016 (Merck), was seemingly developed overnight, work began on that vaccine in the 1990s. Many of the same political, social, financial, and scientific pressures that quickly brought Ervebo to clinical trials and ultimately to market are in full force today, pressing on COVID-19 vaccine research and development.
While many see the race results for a safe and effective vaccine as the silver bullet for COVID-19, medical science and history both suggest this might be overly optimistic. While vaccines have prevented more deaths, permanent disability, and significant illness than any other medical treatment4, they are not magical. Some are more effective than others. The Centers for Disease Control and Prevention (CDC) define vaccine effectiveness as preventing outpatient medical visits. Most vaccines are 90 – 95% effective, with the exception of mumps and pertussis vaccines, which range from 75 – 80% effectiveness. Some, like the measles component of the MMR vaccine, is 99% effective (with two doses).
Seasonal influenza vaccines are less so, ranging from 40 – 60% effectiveness. The 2018-2019 flu vaccine had a meager 29% effectiveness, whereas the 2019-2020 vaccine was 39% effective. Seven approaches are being taken to design COVID-19 vaccines: inactivated virus, live attenuated virus, DNA, RNA, non-replicating viral vectors, replicating viral vectors, and protein subunits. The effectiveness of those that make it to market may vary.
Two vaccines are in the final stages of testing; the clinical trials of one (AZD1222, AstraZeneca) were put on hold in the second week of September after a severe adverse reaction occurred in one UK study participant. A Russian vaccine was approved prior to complete testing, and more than 130 vaccines are currently in the early stages of testing worldwide.
The process of testing a vaccine has three phases, with a fourth phase of continued study once the vaccine is approved for widespread use5. Phase I tests vaccine safety on human subjects, typically involving 20 to 80 people. Phase II involves several hundred people and tests a vaccine's effectiveness, or how well the vaccine does at preventing disease; it's dosing and delivery methods.
Phase III involves tens of thousands of patients (often 50,000 or more) and serves to determine safety, efficacy and detect side effects that might not be seen with smaller groups. In general, the whole process typically takes 18 months or more; hence, the speed with which COVID-19 vaccines are moving through the pipelines is nothing short of amazing. When you exclude vaccines targeting cancers, the overall likelihood for success of a vaccine6 that makes it to Phase I trials is 33.4%, far better than the dismal 13.8% likelihood of a new drug making it to market. This explains why pharmaceutical companies take more interest in vaccines than drugs.
Once a COVID-19 vaccine makes it to market, which may happen before the end of 2020, distribution becomes the next challenge. Most vaccines currently in clinical trials require two doses, spaced at least a month apart; virtually all are injectable vaccines.
It is too early to tell whether they will work equally well on the entire population; older adults need high-dose flu vaccines or a booster ingredient (called an adjuvant) to increase their effectiveness as they have less robust immune systems. Vaccine hesitancy is sure to play a role; unknown portions of the population will likely be reluctant to get a COVID-19 vaccine.
Manufacturing is another challenge – there will most certainly not be enough vaccine for everyone, at least initially. It appears, in the United States at least, that first responders will be in the first group eligible for vaccines. The ability to deliver vaccines to everyone who needs and wants them is certain to challenge our health care system and likely will pull EMS providers into the distribution picture, as has happened in the past. Departments should start to consider how to work with Public Health to vaccinate members and their families, as well as what resources exist for mass vaccination of the rest of your community.
One thing is for certain, given the history of vaccine development: approval of COVID-19 vaccines will not be an end to the pandemic but rather serve as the beginning of what promises to be a challenge to mass distribution efforts and the start of developing some immunity to a virus that has left no place on our planet untouched for the past year. It will not spell the end of other measures implemented to stop the spread of COVID-19 but rather add to the tools we have in our toolbox to protect ourselves, our families, and our communities from harm.
- Failure to vaccinate and vaccine failure (Editorial). Nat Microbiol. 2019; 4: 725. https://doi.org/10.1038/s41564-019-0450-5.
- Francis DP. Successes and failures: Worldwide vaccine development and application. Biologicals. 2010; 38:523-528. https://doi.org/10.1016/j.biologicals.2010.06.003.
- Zaidi MB, Flores-Romo L. The Growing Threat of Vaccine Resistance: a Global Crisis. Curr Treat Options Infect Dis. 2020; 12:122–134. https://doi.org/10.1007/s40506-020-00219-4.
- Greenwood B. The contribution of vaccination to global health: past, present, and future. Philos Trans R Soc Lond B Biol Sci. 2014;369:20130433. https://doi.org/10.1098/rstb.2013.0433.
- College of Physicians of Philadelphia. Vaccine development, testing, and regulation. January 2018. [on-line] available at: www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation.
- Singh K, Mehta S. The clinical development process for a novel preventive vaccine: An overview. J Postgrad Med. 2016;62:4-11. https://doi.org/10.4103/0022-3859.173187