With thousands of articles published weekly on COVID-19, navigating the literature on this emerging infectious disease can be daunting. To help health care professionals and the general public keep up and to fight medical misinformation, a group of emergency physicians started the website Brief19.com, which publishes analysis of COVID-19 research and policy five days a week, all for free. Here are highlights from recent Briefs. (Note: ACEP Now’s medical Editor in Chief, Jeremy Samuel Faust, MD, MS, MA, FACEP, is also Editor in Chief of Brief19.)
Explore This IssueACEP Now: Vol 39 – No 11 – November 2020
Face masks, face shields, and social distancing are likely our new normal for the foreseeable future. The prospects of achieving herd immunity in the United States without a vaccine appears grim.1 The literature on SARS-CoV-2 vaccine development is growing, with approximately 248 candidate vaccines at the time of this writing.2 Nevertheless, there are several fundamental concepts regarding vaccine development for SARS-CoV-2 that are broadly applicable and important to understand.
The Ideal Vaccine
An ideal vaccine should be effective in preventing symptomatic disease (eg, measles, mumps, and rubella vaccine), significantly reducing illness severity (eg, seasonal influenza vaccine), or preventing seroconversion to prevent infection altogether.3,4 The ideal vaccine is multivalent and provides long-lasting immunity. The World Health Organization (WHO) recommends that effective vaccines should show a risk reduction of at least 30 percent.5
The ideal vaccine should be safe, ranging from no side effects to relatively minor side effects, such as headache, low-grade fever, injection site reaction, and myalgias.
Finally, the ideal vaccine should be cost-effective, be easy to administer, require a minimum number of administrations, and not require special storage conditions.4,6
The development of safe and effective pharmaceuticals takes, on average, 13 years from the time of discovery to Food and Drug Administration (FDA) approval.7 The overall failure rate of pharmaceuticals to make it through this entire process exceeds 95 percent. In the late spring, it was estimated that a SARS-CoV-2 vaccine would be available within 12 to 18 months.8 While such estimates were seen by many as naive idealism, there are a few reasons such a timeline now looks more likely. Let’s dive in.
To begin, let’s identify important questions in the vaccine life cycle, which include:9
- Which antigens produce an immune response? (preclinical studies)
- How safe is the vaccine? (Phase I clinical trials)
- What dose is required for immunity? (Phase II clinical trials)
- How effective is the vaccine? (Phase II and III clinical trials)
- What is the long-term safety and efficacy in the general (heterogenous) population? (Phase IV clinical trials)
Thankfully, SARS-CoV-2 vaccine development is not starting from scratch. Attempts to develop a vaccine for coronavirus have been ongoing for years. Numerous groups have worked on a vaccine since the MERS-CoV and SARS-CoV epidemics.10
Another way researchers are attempting to accelerate vaccine development is by repurposing drugs. In a recent paper published in Nature, researchers used an open-access drug library to identify 21 different drugs that can inhibit replication of the SARS-CoV-2 virus in mammalian cell-based assays in a dose-response manner.8
One way to increase the odds of winning the vaccine lottery is by testing myriad potential vaccines at the same time across the globe rather than putting all efforts into just one. At the time of this writing, there are 49 different SARS-CoV-2 vaccines in various clinical trial phases, according to the London School of Hygiene & Tropical Medicine’s VaC COVID-19 vaccine tracker. Ten of those candidate vaccines are in Phase III clinical trials. Additionally, there are currently 199 vaccine candidates in the preclinical phase.
The WHO Solidarity vaccine trial is a global effort that is testing multiple vaccines in geographically diverse regions with high incidence and attack rates of COVID-19 through fixed and mobile research sites. Researchers estimate that a vaccine that halves risk should show efficacy within three to six months of a trial in these highly endemic areas.
Vaccine Types for COVID-19
Let’s look at the landscape of the potential vaccines being investigated. The main categories of candidate vaccines include nucleic-acid vaccines (DNA versus RNA vaccines), nonreplicating viral vectors vaccines, virus vaccines (live attenuated viruses versus inactivated viruses), and protein-based vaccines (subunit vaccines with antigenic fragments).11 Table 1 shows the advantages and disadvantages of each of these categories.
Table 1: Overview of Candidate COVID-19 Vaccine Categories
|Vaccine Type||Number of Doses||“Speed”*||Scalability||Safety||Other Comments|
|Nucleic-acid||Multiple||Fast||Low to medium||Safe||Fastest to develop|
|Viral vector||Single||Medium||High||Safe||Requires booster|
|Live-attenuated virus||Single||Slow||High||Slightly higher risk||Most potent immunogenic vaccines|
|Inactivated virus||Single||Fast||Medium to high||Safer|
|Protein-based||Multiple||Medium to fast||High||Safe||Induce elevated levels of neutralizing antibodies|
*How quickly the vaccine can become available under emergency conditions.
Adapted from Calina et al and Jeyanathan et al.
Briefly, the 10 candidate vaccines in Phase III clinical trials include two nucleic-acid vaccines (mRNA), four viral vector vaccines (adenovirus-based), one protein-based (recombinant coronavirus proteins plus an adjuvant), and four virus vaccines (three inactivated virus, one live attenuated virus). The one live attenuated virus vaccine in a Phase III clinical trial is using the old Bacillus Calmette-Guérin vaccine.
Who Should Get the Vaccine First
A few major organizations, such as the WHO and the US National Academies of Sciences, Engineering, and Medicine, recommend prioritizing health care workers and those with frontline jobs.12 Of course, when the vast majority of health care workers in the United States are white, this promotes structural health disparities by depriving those who have been disproportionately impacted by the virus of a potentially effective vaccine.13 Expanding this to all workers in health care facilities would be a step in the right direction.
What to Do Until a Vaccine Is FDA Approved
Face masks, social distancing, hand washing, large crowd avoidance, and personal protective equipment are the non-vaccine vaccines. They work, and they are easy to do. Until we have a safe, effective, and available vaccine, don’t let your guard down.
- Fontanet A, Cauchemez S. COVID-19 herd immunity: where are we? Nat Rev Immunol. 2020;20(10):583-584.
- Parker EPK, Shrotri M, Kampmann B. Keeping track of the SARS-CoV-2 vaccine pipeline. Nat Rev Immunol. 2020;20(11):650.
- What are the benefits of flu vaccination? Centers for Disease Control and Prevention website. Available at: https://www.cdc.gov/flu/prevent/vaccine-benefits.htm. Accessed Oct. 29, 2020.
- Calina D, Sarkar C, Arsene AL, et al. Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development [published online ahead of print Oct. 1, 2020]. Immunol Res. doi:10.1007/s12026-020-09154-4.
- WHO target product profiles for COVID-19 vaccines. World Health Organization website. Available at: https://www.who.int/publications/m/item/who-target-product-profiles-for-covid-19-vaccines. Accessed Oct. 29, 2020.
- Ada GL. The ideal vaccine. World J Microbiol Biotechnol. 1991;7(2):105-109.
- Collins FS. Reengineering translational science: the time is right. Sci Transl Med. 2011;3(90):90cm17.
- Riva L, Yuan S, Yin X, et al. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. 2020;586(7827):113-119.
- Overview, history, and how the safety process works. Centers for Disease Control and Prevention website. Available at: https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html. Accessed Oct. 29, 2020.
- Begum J, Mir NA, Dev K, et al. Challenges and prospects of COVID-19 vaccine development based on the progress made in SARS and MERS vaccine development [published online ahead of print Aug. 20, 2020]. Transbound Emerg Dis. doi:10.1111/tbed.13804.
- Jeyanathan M, Afkhami S, Smaill F, et al. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615-632.
- Subbaraman N. Who gets a COVID vaccine first? Access plans are taking shape. Nature. 2020;585(7826):492-493.
- U.S. Department of Health and Human Services, Health Resources and Services Administration, National Center for Health Workforce Analysis. Sex, Race, and Ethnic Diversity of U.S. Health Occupations (2011-2015), Rockville, Maryland. 2017.
Dr. Niforatos is an emergency medicine resident at the Johns Hopkins School of Medicine in Baltimore and research editor of Brief19.com. Follow him on Twitter @ReverendofDoubt and follow Brief19 @Brief_19.