COVID-19 Vaccine Development [Updated on June 29, 2021] (GAO-20-583SP)

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A GAO Science & Tech Spotlight on COVID-19 vaccine development, GAO-20-583SP, updated on June 29, 2021, from GAO's Science, Technology Assessment, and Analytics team. It explains how vaccines trigger the immune system to produce antibodies and why developing a safe, effective vaccine is a complicated, costly and typically lengthy process with a historically low success rate. It reports that more than 250 COVID-19 vaccines have been in development globally. The federal government awarded billions of dollars to companies for six vaccine candidates under a partnership between the Departments of Defense and Health and Human Services, and the six candidates use three different platforms.

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Science, Technology Assessment,
JUNE 2021
and Analytics
WHY THIS MATTERS
SARS-CoV-2, which causes COVID-19, has killed
millions worldwide. Vaccines can help save lives and
SCIENCE & TECH SPOTLIGHT: speed economic recovery. Developing a safe, effective
vaccine is a complicated, costly, and typically lengthy
COVID-19 VACCINE process that has historically had a low success rate.
U.S.-funded efforts have made several vaccines
DEVELOPMENT available to the public in record time.

/// THE TECHNOLOGY MIT study. There has been an effort to expedite this process for COVID-19
vaccines. More than 250 COVID-19 vaccines have been in development
What is it? Vaccines protect people from disease by triggering the globally. Of those, the federal government awarded billions of dollars to
immune system to produce antibodies that will fight the pathogen companies for the development, manufacture, or distribution of six vaccine
attacking the body. In the case of COVID-19, the pathogen is the virus candidates under a partnership between the Departments of Defense
SARS-CoV-2. Developing a vaccine is an expensive and typically lengthy (DOD), and Health and Human Services (HHS). These six candidates use
process because it involves a rigorous series of steps to first identify a three different “platforms,” or mechanisms to prompt the body to produce
potential vaccine “candidate,” then assess it for safety and effectiveness. antibodies (fig. 2). The three platforms generate proteins that mimic part of
Billions of vaccine doses designed to fight COVID-19 have already been the spike protein found on the surface of SARS-CoV-2. The spike protein
administered as of June 2021 across the U.S. and the world, and death alone does not cause a COVID-19 infection but may be sufficient to
rates in some countries have dropped dramatically. produce an immune response.
How does it work? A vaccine can use a pathogen that has been modified
to be safe or a molecule that resembles a part of the pathogen, triggering
the immune system to produce antibodies. If the vaccinated person is
exposed later to the pathogen, their body will produce those antibodies
again, increasing their chances of fighting off infection.

Development starts with identifying a pathogen “target,” such as a protein,
that can induce an immune reaction. Researchers create a vaccine
candidate similar to that target that will induce production of antibodies
effective against the pathogen. The vaccine candidate moves through
stages of development, assessment, authorization, and licensure (fig. 1).

Figure 2. COVID-19 vaccine candidates use different mechanisms, such as those shown
above, to prompt the body to produce antibodies against SARS-CoV-2.

The first platform uses a molecule called mRNA, which is specifically
coded to generate proteins that induce an immune response. This is a
newer method of vaccine development.

The second platform uses recombinant proteins, which are produced
by genetically engineered bacteria or other cells, to induce an immune
response. This platform is already being used successfully against other
viruses, such as the human papillomavirus (HPV), which can cause
cervical cancer.

The third platform uses another virus—called adenovirus—removed of
its infectious aspects, making it safe as a “vector” to deliver a piece of
a pathogen to produce proteins that induce an immune response. This
platform is being used in U.S. clinical trials for HIV and Ebola vaccine
candidates.

How mature is it? The process for developing a new vaccine as
Figure 1. Example of a COVID-19 vaccine timeline. Specific steps and timelines may outlined by the Food and Drug Administration (FDA) is well established.
vary. According to FDA, any COVID-19 vaccine that initially receives an emergency use
In the exploratory stage, the pathogen target and candidate vaccine are
authorization is expected to be reviewed and licensed through a biologics license application.
identified. In the preclinical stage, researchers use cells and animals to
Under normal circumstances, the entire process typically takes 10 to 15 assess safety and produce evidence of clinical promise, evaluated by the
years, with more than 65 percent of candidates failing, according to an candidate’s ability to elicit a protective immune response.

GAO-20-583SP COVID-19 Vaccine Development
Science, Technology Assessment,
and Analytics

During clinical trials, the number of people participating is increased ■ Data limitations. According to FDA, as with all licensed vaccines,
at each successive phase. Safety, efficacy, proposed doses, schedule there can be limitations in safety data obtained from pre-licensure
of immunizations, and method of delivery are evaluated. Clinical trials clinical trials of a COVID-19 vaccine. For example, the clinical trials
can be terminated for various reasons, including observations of side may not be large enough to detect rare adverse reactions.
effects considered to be serious adverse events. For some COVID-19
■ Manufacturing constraints. A shortage of manufacturing capacity
vaccine candidates, large-scale manufacturing began during clinical trials
may lead to production bottlenecks. Manufacturing supply chains
so that doses could be available for distribution upon emergency use
have been strained by global demand for certain vaccine ingredients
authorization (EUA) of the vaccine.
and equipment during the COVID-19 pandemic. In addition, personnel
FDA authorizes and licenses vaccines to be marketed in the U.S. with specialized skills are needed to run manufacturing facilities.
Following a declared emergency, FDA can issue EUAs to allow temporary
use of vaccine candidates that have not yet been licensed, provided /// POLICY CONTEXT AND QUESTIONS
certain statutory criteria are met. For example, it must be reasonable to ■ What mechanisms are most effective for quickly scaling up vaccine
believe that the vaccine may be effective and that the known and potential manufacturing, production, and distribution?
benefits of the vaccine outweigh the known and potential risks. FDA’s
role includes oversight of manufacturing and continual monitoring after ■ What could improve the scientific understanding of unknowns such
authorization or licensure. as how long vaccines protect people, and how safe and effective
they are in certain populations, such as young children?
FDA has four programs to facilitate and expedite the development
and review of new vaccine candidates for the prevention of serious or /// SELECTED GAO WORK
life-threatening conditions such as COVID-19. These programs can
help expedite some processes, such as a rolling review of portions of In addition to ongoing work, GAO has issued the following products
applications, to bring vaccines to market more quickly. Vaccine developers related to COVID-19 vaccines as well as an earlier version of this product.
could use one or more of these programs.
■ Operation Warp Speed: Accelerated COVID-19 Vaccine
/// OPPORTUNITIES Development Status and Efforts to Address Manufacturing
Challenges, GAO-21-319.
Several technologies and initiatives offer opportunities to accelerate ■ Coronavirus Oversight: Operation Warp Speed Dashboard.
vaccine development. For example: https://ows.gaoinnovations.gov.
■ Genomic tools. Tools that provide information about a pathogen’s ■ COVID-19: Federal Efforts Accelerate Vaccine and Therapeutic
genetic makeup can make it easier for researchers to quickly select Development, but More Transparency Needed on Emergency Use
a target that can trigger an immune response. Authorizations, GAO-21-207.
■ Collaboration and partnerships. DOD and HHS are working /// SELECTED REFERENCES
with companies and manufacturing partners to help accelerate the
development, manufacture, and distribution of COVID-19 vaccines. Department of Health and Human Services. Food and Drug Administration. Development
and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry. June 2020.
■ Multiple vaccine mechanisms. Simultaneous testing of multiple
vaccine mechanisms can improve the chances of developing a Le, Tung T., Zacharias Andreadakis, Arun Kumar, Raúl G. Román, Stig Tollefsen, Melanie
successful vaccine faster. Saville, and Stephen Mayhew. “The COVID-19 vaccine development landscape.” Nature
Reviews Drug Discovery, vol. 19 (2020): pp. 305-306.
/// CHALLENGES
This product, issued in June 2021, is an update to the COVID-19 Vaccine
■ Virus mutations. Coronaviruses, such as SARS-CoV-2, can Development Science & Tech Spotlight issued in May 2020.
mutate and potentially reduce or eliminate a vaccine’s effectiveness,
potentially creating a need for new vaccines.

GAO SUPPORT: This document is not an audit product. With science and technology constantly
evolving at a rapid pace, it is subject to revision as appropriate. It contains
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GAO staff are available to brief on completed bodies of work or specific reports Scientist of the U.S. Government Accountability Office.
and answer follow-up questions. GAO also provides targeted assistance on This is a work of the U.S. government and is not subject to copyright protection in
specific science and technology topics to support congressional oversight activities the United States. The published product may be reproduced and distributed in its
and provide advice on legislative proposals. entirety without further permission from GAO. However, because this work may
Timothy M. Persons, PhD, Chief Scientist, personst@gao.gov contain copyrighted images or other material, permission from the copyright holder
may be necessary if you wish to reproduce this material separately.
Staff Acknowledgments: Karen Howard (Director), Sushil Sharma (Assistant
Director), Laura Holliday (Assistant Director), Chi Mai (Analyst-in-Charge), Louise
Fickel, Eliot Fletcher, Cindy Korir-Morrison, and Anika McMillon.

GAO-20-583SP COVID-19 Vaccine Development

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