Why don’t we have a COVID-19 vaccine — yet?

We are all appreciative for the hard work and time medical professionals and scientists are committing to end the pandemic. When the virus was detected in Dec 2019, China had identified several candidates to become possible vaccines by Jan 2020. As of May, there are a few companies that have a vaccine in phase 2 human testing, but a safe vaccine is still months away. You might be thinking, “What’s taking so long?” The reason is much more complicated than you think — vaccines are an expensive and time-consuming venture. Even after a vaccine is created and validated it may be too late for it to be useful. Today’s blog post will discuss why a new vaccine takes so long, how it is made, and the economics behind an emergency vaccine.

What is a Vaccine?

This picture from the Well Come Collection (wellcomecollection.org) is titled “Hypodermic syringe, Record type, by Hawkins, London (A500633/1), together with bottle of diphtheria vaccine (A629753/1). Front three quarter view, dark grey background.”

Our blog discussing vaccines has a detailed description of what they are, but we’ll give a short recap here. Vaccines are essentially a non-active version of some pathogen. The difference between types of vaccines relies upon how much and what part of the pathogen is utilized. For example, the traditional vaccines called whole pathogen vaccines contain the entire pathogen which has been killed (inactivated vaccines) or weakened (live-attenuated vaccines). Next generation vaccines, such as subunit vaccines and nucleic acid vaccines, use only the components that stimulate the immune system ( i.e. antigens) or the genetic material that encodes these antigens [1]. Vaccines take advantage of your body’s adaptive immune system to create antibodies that would fight off the virus before it spreads too far within the body. This is the main reason why vaccines are such a powerful tool — they prevent diseases [2].

When a potential vaccine is identified, the testing phase begins. The main goal of preclinical research is to assess the toxicity through in vitro (cells in the lab) and in vivo (animal testing) assays. Finding an animal that can be infected by a disease takes a lot of time. However, susceptibility studies help identify the right animal model for a disease. In the case of SARS-CoV-2, these studies have shown that ferrets and cats are promising candidates [3]. Once the preclinical assessment of the vaccine has been done in the animal model, the next step is to move on to clinical research or human trials. There are 3 phases in human trials [4, 5].

Phase 1 Safety and Immunogenicity

Phase 1 involves testing and closely monitoring 20–100 healthy subjects. In this first step, scientists usually learn the relationship between the dose size and the side effects. If there are no serious side effects, the vaccine moves to phase 2.

Phase 2 Dose-ranging

Phase 2 involves testing and monitoring hundreds of subjects with the condition. Studies in this phase focus on gathering information on how the dose size relates to the immune response.

Phase 3 Efficacy, Side effects and Adverse reactions

Phase 3 involves testing and monitoring thousands of patients and collecting critical documentation on effectiveness and safety data. In this step, subjects who have been vaccinated are compared with subjects that received a placebo or a different vaccine.

The effectiveness does not need to be 100% — in fact, the average effectiveness of vaccines is 80%. If the vaccine is safe, exhibits a minimum amount of side effects, and there is a high percentage of it working, it will move on to the distribution phase.

During the distribution phase the appropriate amount of doses are manufactured to distribute to pharmacies and hospitals. Although the process is straightforward, the preparation for these facilities is based on the market for the vaccine. For example, 40 million people in the U.S. contract influenza each year which creates a demand for the flu vaccine. With a predictable market, companies will plan for the next year’s flu strain, develop a vaccine, and manufacture the needed amount. Unlike annual vaccines, pandemics do not have any sort of private preparation. Vaccines simply take too long to develop — even if they’re rushed — to be highly effective during pandemics. The peak of cases will be long-since passed by the time manufacturers distribute the product. This happened in 2009, when the H1N1 virus swept across the globe. An immense effort was taken to develop a vaccine, but it wasn’t ready until the following year. The virus had already started to slow down by this time. Thus, millions of samples of the vaccine were stored and eventually discarded. This was at great revenue loss to manufacturers. In an NPR report they spoke to the former head of Biomedical Advanced Research and Development Authority or BARDA, Rick Bright, who described how the government has taken on the burden of emergency vaccine development and production.

How are vaccines produced?

In this 2019 photo, a Centers for Disease Control and Prevention (CDC) scientist uses a syringe to inject flu virus into fertilized chicken eggs, where they will grow and multiply. Viruses are then isolated from these eggs for use in a variety of additional laboratory tests [6].

There are secret government chicken farms in undisclosed locations across the U.S. After the 2001 Anthrax attacks, these farms were established in response to biothreats and to manufacture emergency vaccines. Chicken eggs are used as incubators to grow viruses because viruses need a cell to replicate — they can’t be cultured like bacteria or fungi. After the incubation period, the virus is separated from all the growth materials (egg white). It is then passed through chemical and ultrafiltration systems to further purify it. Finally, the pathogen is weakened or deactivated and packaged for distribution. The facilities are not allowed to disclose the amount of eggs they produce but it is estimated that nearly 900,000 eggs are needed a day to create enough vaccines for the US population alone. After a vaccine is found, the government awards the companies with a guarantee to purchase their product even if there is no longer a need for it. This is the problem, after this arduous process many of the vaccines will never be needed.

Due to the long process of creating a vaccine and the length of effective quarantine measures a vaccine is never created in time. The government has taken steps to incentivize companies to produce a vaccine anyway by having year-round production facilities and guarantee purchase of the vaccines. There are talks of the World Health Organization and the Coalition for Epidemic Preparedness Innovations to administer programs that monitor potential viral outbreaks and prepare vaccines in advance — similar to the annual flu vaccine. It is a matter of national security and global security to have these programs in place to ensure a rapid response and one day have a system in place to deliver vaccines when they are needed.

Citations and links:

[1] National Institute of Allergies and Infectious Diseases. “Vaccine Types”. 1 July 2019. Retrieved from https://www.niaid.nih.gov/research/vaccine-types

[2] United States. Dept. of Health and Human Services. Centers for Disease Control and Prevention. “Vaccines: The Basics”. 14 March, 2012. Retrieved from https://www.cdc.gov/vaccines/vpd/vpd-vac-basics.html

[3] Jianzhong Shi et al. “Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2”. Science 2020. Retrieved from https://science.sciencemag.org/content/early/2020/04/07/science.abb7015?rss=1

[4] U.S Food and Drug Administration. “Vaccine Product Approval Process”. 30 January 2018. Retrieved from https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-product-approval-process

[5] U.S Food and Drug Administration. “Ensuring the Safety of Vaccines in the United States”. July 2011. Retrieved fromhttps://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Ensuring-the-Safety-of-Vaccines-in-the-United-States.pdf

[6] United States. Dept. of Health and Human Services. Centers for Disease Control and Prevention. Public Health Image Library. “Vaccine” PNG. Retrieved from: https://phil.cdc.gov/Details.aspx?pid=23203

Welcome to the Macromoltek blog! We're an Austin-based biotech firm focused on using computers to further the discovery and design of antibodies.