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The Anatomy of Potential COVID-19 Vaccines

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November 05, 2020

The Anatomy of Potential COVID-19 Vaccines

Jennifer Morency

picture The Anatomy of Potential COVID-19 Vaccines

It’s been almost a year since the coronavirus pandemic turned the world as we knew it upside down. In January of 2020, Chinese scientists started sharing a virus genome online that was causing a type of pneumonia, which soon turned into the global COVID-19 pandemic.

Since then, it has been a worldwide effort to try and develop a vaccine for COVID-19 and put a halt to the devastating number of cases that continue to rise and the deaths it has taken so far.

The Center for Systems Science and Engineering (CSSE) at Johns Hopkins University have put together a global dashboard of the coronavirus situation. At the time of writing this article, there are over 45.3M COVID-19 cases around the world and 1.18M people have died of the novel virus.

The current state of the situation has pushed experts and governments from many countries to band together to find a vaccine. What normally takes scientists an average of ten years to develop and test a vaccine has been cut exponentially in regards to COVID-19. Experts have been given the audacious goal of producing an effective vaccine within a 12 to 18-month time span. The amount of resources being pooled together globally is unprecedented, propelling the global race forward in developing a working vaccine against the coronavirus.

This article will delve into the current vaccines being developed, their timelines and the potential candidates based on various product categories.

The Crown Jewel of Viruses

The coronavirus SARS-CoV-2, which is the core of the virus, is composed of a protein shell with a single strip of ribonucleic acid (RNS) within it. The genome was made public on January 10, 2020, quickly sparking candidate vaccines.

As the image below illustrates what it looks like, you can see spikes branching out from all around, resembling a form of crown. Hence, from the Latin word “corona” meaning crown in English, the novel virus was named the coronavirus.

coronavirus structure

The spike proteins are how the virus enters a cell by binding to the ACE2 receptor. The virus’s RNA is then read by the cell and newly infected proteins are made and arranged into copies of the virus, which are then released to infect more cells.

Phases of a Potential Coronavirus Vaccine

As of today, there are 213 COVID-19 vaccines currently being developed around the world, 37 of which are now in clinical testing. Normally, vaccine development takes years and requires many steps, from laboratory tests to animal testing to human clinical trials.

With world governments pooling resources, some of these steps are working in parallel to speed up the process. Some animal studies are not yet finished and researchers have already begun human testing, while others are planning ahead to Phase 3 trials while still in Phase 1.

The United States government has itself invested over $8 billion to accelerate the development of a vaccine and jump-start manufacturing before any research is finished or reliable results are established. However, it is important to note that top U.S. government officials have reassured the public by stating that no vaccines will be approved without a Phase 3 trial, while other countries have different standards.

The Food and Drug Administration (FDA) further stated that in order for a vaccine to be approved, it will have to prevent or decrease symptoms in at least 50 percent of the recipients. As a comparison, the Centers for Disease Control and Prevention (CDC) have shared that the flu vaccine’s effectiveness is around 40 to 60 percent.

COVID-19 Vaccine Timeline

There are technically six steps to developing a working vaccine against a known virus. Each of these require extensive work and depend on one another.

Steps Outline
Steps Pre-Clinical Phase Outline
  • Data collection
  • Repetitive non-human testing
  • Evaluation of toxic and pharmacological effects


Steps Clinical Phase I Outline
  • Small study of healthy humans
  • Evaluation of safety and immune responses based on various doses
  • Usual timeline takes 1 to 2 years, coronavirus trials expected to take 3 months


Steps Clinical Phase II Outline
  • Larger study group of 100 humans
  • Safety and efficacy assessments
  • Understanding of optimal dose and vaccine schedule
  • Usual timeline takes 2 to 3 years, coronavirus trials expected to take 8 months


Steps Clinical Phase III Outline
  • Larger study group of 1000 humans
  • Assessments of safety and efficacy
  • Usual timeline takes 2 to 4 years, coronavirus trials could be combined with Phase II


Steps Regulatory Review Outline
  • Trial data and licensing application are reviewed by government agency before approval
  • Can work in parallel with manufacturing
  • Usual timeline takes 1 to 2 years, coronavirus review expected to take a few months


Steps Clinical Phase IV Outline
  • Monitoring effectiveness in real-world conditions
  • Testing starts after the vaccine has been released to the public


This then leads to early manufacturing, which we can see from above can start during the regulatory review stage. It typically starts during this phase as developers will often make sure that a sufficient amount of vaccine doses are ready to be shipped out when approval comes in.

Of course, vaccines are normally manufactured on a much smaller scale than the ones that will be needed for the global distribution of the coronavirus vaccine. This increases the risk for manufacturers in terms of resource losses and incurred risks. Due to this, industries, governments and international organizations are all working together to encourage manufacturing before an official vaccine approval. They want to reduce the risk for manufacturers and ensure resources are ready when and if approval is given.

Current COVID-19 Vaccine Candidates

Vaccine technology have many different categories, all working under the same principle that the dose injected needs to teach the body’s immune system to identify and block a virus. Vaccines have the objective of activating the immune system’s T-helper cells responsible for identifying viruses. These then instruct B-cells to start creating antibodies to block off the virus from being able to copy itself and produce T-killer cells that in turn kill infected cells.

The reason behind there being different categories of vaccines is that not all activate all of these immune responses. Based on various testing agents, some vaccines could activate only a part of the immune responses. The following are the nine current COVID-19 vaccine categories being tested and the candidates currently being developed under each.

Inactivated Virus

This category of coronavirus vaccines has a total of 14 candidates. The virus used for this vaccine is grown in culture and then killed to weaken virulence and prevent infection. This could potentially be given to people with weaker immune systems. Other vaccines that have used this category are polio and influenza.

There are three vaccines in this category that are currently in Phase III of clinical trials (Sinovac/Instituto Butantan, Wuhan Inst./Sinopharm, Beijing Inst./Sinopharm), with three others in Phase II. The Phase III trials for all three vaccine candidates started in July 2020, with all three receiving early approval for emergency use in China in August 2020. Furthermore, two of the Phase III candidates (Wuhan Inst./Sinopharm, Beijing Inst./Sinopharm) also received approval for emergency use in the UAE in September 2020.

The 8 remaining vaccines in this category are all in the Pre-Clinical Phase.

Live Attenuated Virus

This category of COVID-19 vaccines only has four potential candidates. In comparison to the inactivated virus category, the live attenuated virus category uses whole viruses. These viruses are live to lead to a stronger immune response but are also weakened to diminish virulence. Other vaccines that have used this category are measles, tuberculosis and mumps.

All four of the potential candidates are currently in Phase I of clinical trials with no results yet to show.

Protein Subunit

The protein subunit category of coronavirus vaccines has a total of 71 candidates. This vaccine involves introducing a tiny amount of the virus rather than a whole one. The goal is to provoke an immune response and to stimulate immunity. Other vaccines that have used the subunit category include shingles and Hepatitis B.

Currently, there is only one candidate in Phase III (Novavax). It was dosed in October 2020 and was selected for the U.S. Operation Warp Speed in July 2020. The Sanofi Pasteur/GSK vaccine that began Phase I/II in September 2020 was also selected by the U.S. Operation Warp Speed in April 2020. Funding for this vaccine was awarded in July 2020.

Among the four candidates in Phase II clinical trials, one received early approval for use in Russia in October 2020 while Phase I/II for this vaccine started in July 2020.

There are also seven candidates in Phase I and the rest of the 59 candidates in this category are all in the Pre-Clinical Phase. Many of the candidates in the Pre-Clinical Phase have anticipated start dates for Phase I trials at the end of 2020.

Replicating Viral Vector

This category currently has 18 candidates. The replicating viral vector vaccine category involves inserting a viral protein gene into a different virus that can’t cause illness but that can still replicate. This allows it to generate copies of the viral protein that will cause an immune response of that protein. Other vaccines that used the replicating viral vector are the dengue and Ebola vaccines.

Of the 18 candidates in this category, only one has entered Phase I/II, which began in September 2020. The rest of the 17 candidates are in the Pre-Clinical Phase.

Non-Replicating Viral Vector

The non-replicating viral vector category has 26 vaccine candidates. This approach resembles the replicating viral vector vaccine, with the obvious exception of using a non-replicating gene instead of a replicating gene. A viral gene is added to a non-replicating virus and delivered to the vaccine recipient. There are currently no approved products of the non-replicating viral vector to date.

Within this category, there are four candidates that are in Phase III:

  • Janssen Pharma Phase III began in September 2020. It was chosen for the U.S. Operation Warp Speed in February 2020 and was given funding in August 2020.
  • University of Oxford/AstraZeneca Global Phase III trial (UK, Brazil, South Africa, Japan) began in June 2020 and expanded to the U.S. in August 2020. This candidate was selected for U.S. Operation Warp Speed in May 2020.
  • CanSino Biologics Phase III dosed in September 2020 and received early approval for military use in China in June 2020.
  • Gamaleya Research Institute The Phase III (post-registration) trial began in September 2020. It received early approval for use in Russia in August 2020 and mass production of this vaccine is anticipated to begin September 2020.

The rest of the candidates in this category include two in Phase I and twenty in the Pre-Clinical Phase.


This category of COVID-19 vaccines has 17 candidates. This category works on the introduction of viral genetic material (DNA) to cells. It has been dubbed a next-generation vaccine and aims to use DNA to make viral proteins that will generate an array of immune response types. Although this category could potentially develop vaccines at a faster and easier pace than others, there are currently no DNA vaccines that have been approved for human use.

Of the four vaccine candidates in Phase III, the Inovio Pharmaceuticals vaccine joined the U.S. Operation Warp Speed in June 2020. The thirteen other candidates are in the Pre-Clinical Phase.


The RNA-Based vaccine category has a total of 27 candidates. This vaccine introduces genetic material (RNA) to provide immunity. Similar to the DNA-based vaccines, RNA-based vaccines can also potentially be developed faster and more easily than others. There are currently no RNA vaccines that have been approved for human use.

There are two vaccines in this category that are currently in Phase III of clinical trials. The Moderna vaccine started its Phase III COVE study in July 2020. The FDA granted this vaccine the fast-track designation in May 2020. The Moderna vaccine was also selected for the U.S. Operation Warp Speed in April 2020. The other vaccine, BioNTech/Fosun/Pfizer, was also granted fast-track designation by the FDA in July 2020 and was selected for the U.S. Operation Warp Speed in July 2020.

Within the RNA-Based category, there are also three candidates in Phase II and one candidate in Phase I clinical trials. The rest of the 21 candidates in this category are all in the Pre-Clinical Phase.

Virus-Like Particle

There are currently 16 candidates in this category. The virus-like particle vaccines are non-infectious as they have no viral genetic material. They are a safer alternative to attenuated viruses as they cannot replicate. A current vaccine that uses virus-like particles is the HPV vaccine.

One of the vaccine candidates in this category is expected to start Phase II/III in October 2020, while the other started Phase I/II in September 2020. The rest of the 14 candidates are in the Pre-Clinical Phase.

Other Vaccines

There are 18 vaccines that fall under this category. These include vaccines that either do not have publicly disclosed details about their category or they include things such as a self-assembling vaccine or gene-encoded antibodies, all of which are difficult to classify within the previously mentioned categories. All 18 of the vaccines that fall within this category are in the Pre-Clinical Phase.

graph categories candidates vaccine Covid 19

What Does the Future Look Like?

One thing is safe to say, billions of dollars are being pooled around the world to expedite the COVID-19 vaccine creation. However, nobody can safely say exactly when that will be and what the vaccination timeline will be for different countries around the world.

In conjunction with clinical trials and the development of a vaccine, there are also medical products being developed to treat the coronavirus. This allows patients that contract COVID-19 to receive treatments that can help them cope with the virus while a vaccine is being developed. These treatments include newly identified drugs as well as current medicine that treat other diseases.

The globally anticipated coronavirus vaccine demands enormous amounts of fundraising and international cooperation. It also requires an immeasurable amount of work from academic labs, scientists, drug developers and many other organizations and people. It’s a worldwide effort that is bringing people together while safely asking them to stay apart.