Johnson and Johnson’s COVID-19 Vaccine: How Does It Work?

By Nidhi Parekh of The Shared Microscope

Update, February 27, 2021: The Johnson and Johnson vaccine has been granted Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA). This means it is on the commercial market in the United States and can be administered to patients. The J&J vaccine is the third COVID-19 vaccine to receive an FDA EUA, behind Pfizer (which was #1 in the US vaccine race) and Moderna (#2).

Learn about the Johnson & Johnson COVID-19 vaccine developed by J&J subsidiary Janssen in this post.

In this post by @TheSharedScope, read about how the Johnson and Johnson #COVID19 vaccine works. $JNJ

Check out other posts in our COVID-19 vaccine series:
[Moderna | Oxford/AstraZeneca | Pfizer/BioNTech | Johnson & Johnson | Novavax | Sinovac]

Table of Contents:

Johnson & Johnson Is Not New to Infectious Disease Vaccine Development

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Johnson & Johnson (J&J) is one of the many pharmaceutical companies throwing their hat in the ring to develop a COVID-19 vaccine. The J&J vaccine is, like many others in the COVID-19 vaccine race, a not-for-profit vaccine developed for emergency use in the novel coronavirus pandemic.

This is not the first time J&J is making large-scale vaccine development efforts. The company has mobilized in response to other viruses: most notably, Ebola, Zika, and HIV. Their Ebola vaccine has recently received approval for commercial use in the European Union. Their HIV and Zika virus vaccines remain in development. J&J created a vaccine platform used for the development of these vaccines, which they are also using in their development of a COVID-19 vaccine.

The J&J COVID-19 investigational vaccine currently goes by two names — JNJ-78436735 or Ad26.CoV2-S. The vaccine is developed by J&J’s pharmaceutical arm, Janssen.

Keep reading to learn more about the J&J COVID-19 vaccine, its development, and ongoing clinical trials.

photo of gloved person holding up a globe wearing a facemask
Photo from Pexels.com

The SARS-CoV-2’s Spike Protein Interacts with Our Cells to Cause COVID-19 Infection

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The virus that causes COVID-19 is called SARS-CoV-2. Let’s quickly review some basic facts about SARS-CoV-2, its structure, and how it causes a COVID-19 infection, before we get into the discussion of the J&J vaccine. 

The most characteristic features of the SARS-CoV-2 virus are spiky protrusions found on the virus’s surface. These spiky things are called spike proteins. We have covered the SARS-CoV-2 spike protein in our series of COVID-19 vaccine articles. Here, we will only cover the basics to ensure the rest of the article is clearly understood. To learn more detail about the COVID-19 infection mechanism via the SARS-CoV-2 spike proteins, check out our previous post here.

The SARS-CoV-2 spike proteins are essential for the virus to be able to infect human cells. Without these spike proteins, the virus does not have a way into the cell, where it takes over the cellular machinery and makes more copies of itself. This process, by which the virus replicates, is what causes a COVID-19 infection.

The fusion process of the spike protein to the human cell causes the spike protein to change conformation (shape). The spike protein is in the pre-fusion conformation before it fuses with the human cell. During fusion, the virus empties its contents into our cells, and can take over control of the cell. After the virus’s spike protein has fused with the cell, its spike protein conformation changes to what is called the post-fusion conformation.

illustration of SARS-CoV-2 spike protein's conformational change after binding to a host cell

After the SARS-CoV-2 spike protein fuses with a human cell – one of the first steps leading to a COVID-19 infection – the spike protein undergoes a change in shape. Illustration by The Shared Microscope

The J&J COVID-19 Vaccine Contains a Pre-Fusion Version of the SARS-CoV-2 Spike Protein

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Knowing about the pre-fusion and post-fusion conformations of the SARS-CoV-2 spike protein is important. Several COVID-19 vaccines, including the J&J vaccine and also the Pfizer/BioNTech vaccine, rely on the pre-fusion version of the spike protein, rather than the post-fusion version. The pre-fusion form of the spike protein is the version that would bind to human cells and, in doing so, cause COVID-19 infection. The idea here is that, by establishing immunity to the specific form of the spike protein that gets into human cells and causes COVID-19 infection, we can fend off a COVID-19 case.

The J&J vaccine uses the pre-fusion spike protein conformation to train our body to identify the SARS-CoV-2 spike proteins and fight the virus as soon as it is introduced into the human body. This training will ensure that the spike protein does not come in contact with our cells when exposed to it naturally — introducing a preventative barricade at the very start of the infection mechanism.

J&J’s Vaccine for COVID-19 Is a Viral Vector Vaccine

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A viral vector is a means of delivering antigens into the body to develop immunity to them. An antigen is a molecule which exists on the surface of a pathogen — for example, SARS-CoV-2’s spike proteins. Once the antigen is introduced into the body, the immune system works to neutralize and establish immunity to the antigen.

Both the Johnson and Johnson and Oxford/AstraZeneca vaccines for #COVID19 are examples of viral vector vaccines. $JNJ $AZN

A viral vector vaccine is a “mashup” of two viruses. Just how does a viral vector vaccine work? As we wrote in our post about the Oxford/AstraZeneca vaccine

“Just take a virus, take out the parts that cause infection, add parts from another virus that do not cause infection (but do help you build immunity to that other virus), and voilà — you’ve got a viral vector which has some properties of both viruses, but is neither of those viruses…[and] cannot cause disease.”

To learn more about how viral vector vaccines work, check out our discussion of the Oxford/AstraZeneca viral vector vaccine here.

We will talk more about the specifics of how J&J has developed this viral vector vaccine in the next section. To summarize, the J&J COVID-19 vaccine uses the pre-fusion form of the SARS-CoV-2 spike protein as the antigen of interest. To create the viral vector, this part of the novel coronavirus is cut-and-pasted into a human adenovirus. The resulting viral vector contains the genetic information needed for our immune system to develop antibodies to SARS-CoV-2 without being infected with the virus. This viral vector comprises the J&J vaccine.

AdVac: J&J’s COVID-19 Vaccine Technology

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J&J’s COVID-19 vaccine uses subsidiary Janssen’s cutting-edge AdVac vaccine manufacturing platform. According to the Janssen website, AdVac is “a technology based on the development and production of adenovirus vectors (gene carriers).” The AdVac technology was used in the development of their Ebola vaccine, which was approved by the European Commission in July 2020, and, since then, has been deployed in the Democratic Republic of Congo and Rwanda. According to Janssen, AdVac enables rapid adenovirus-based vaccine development in response to emerging disease epidemics in a manner that is both cost-effective and large-scale.


The J&J vaccine uses AdVac’s adenovirus vector technology.  In this viral vector vaccine, a portion of the SARS-CoV-2’s genetic information is cut-and-pasted into a human adenovirus called adenovirus26 (Ad26). The Ad26 virus serves as the viral vector here; it causes symptoms of the common cold in humans. For the J&J COVID-19 vaccine, the Ad26 virus has been modified so that it cannot replicate and cause disease. In J&J’s COVID-19 vaccine, the Ad26 vector is combined with the SARS-CoV-2 spike protein for efficient delivery of this protein to our bodies to establish immunity to it.

The AdVac vectors use an adenovirus as a carrier for the genetic code of the SARS-CoV-2 pre-fusion spike protein. As mentioned before, the adenovirus is edited so that it is unable to replicate or cause disease in humans – it is like an empty capsule that on its own has no use. The most important part of the AdVac technology is what is inserted into this capsule. In this case, what’s inserted into the adenovirus is the SARS-CoV-2 pre-fusion spike protein — the important piece of the J&J vaccine technology that renders immunity to the novel coronavirus. 

When the body encounters the antigen — that is, the genetic code of the SARS-CoV-2 spike protein — that is encapsulated within the adenovirus vector technology (AdVac), it invokes an immune response. This response helps the body induce a long-lasting immune response involving both immune cells and antibodies. This is vital for short-term as well as long-term immunity. 

If in the future, the body encounters the SARS-CoV-2 spike protein, our body will be able to respond to the virus faster and more effectively, as the immune system will have already had a practice round when injected with the vaccine. Next time the SARS-CoV-2 virus comes around, the body will be able to quickly and effectively recruit immune cells and antibodies to prevent the pathogen from inducing any disease.

To learn more about Janssen’s AdVac technology, we recommend watching this video:

What Data Is There on the J&J Vaccine?

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The J&J COVID-19 vaccine uses the AdVac technology explained above. It is a non-replicating human adenovirus 26 vector expressing a pre-fusion spike protein from the SARS-CoV-2 virus. 

J&J’s vaccine was first trialed on monkeys in early July. These results looked promising. Trials were then conducted in close to 1,000 healthy individuals aged over 18 years. This trial was backed by the U.S. government as part of Operation Warp Speed.

According to Reuters, J&J’s investigational COVID-19 vaccine produced a strong immune response against the novel coronavirus. The vaccine was well tolerated at two different doses, and may only require a single dose.

Interim results from Phase 1/2 results reported mild to moderate side effects to the vaccine, which include a fever, and pain at the injection site, fatigue, headache and myalgia (muscle aches and pain). 

The J&J ENSEMBLE study

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The ENSEMBLE trial refers to the final stage of the J&J vaccine trial before FDA approval (Phase 3). The purpose of the ENSEMBLE trial is to determine the safety and efficacy of the investigational J&J vaccine. It is currently being evaluated in people aged 18 years or older, including a significant number of participants representing the 60 years and older age group. Currently, around 60,000 people around the globe are partaking in the J&J COVID-19 vaccine trial, which makes it the largest Phase 3 clinical trial in the COVID-19 vaccine race. 

Participants will be in the study for approximately two years plus one month. During this time, the participants will have up to eight visits with a study doctor or clinical research staff. The participants will also continue to fill out several tests and assessments including questionnaires, physical examinations, and medical tests to monitor their vital signs. 

The ENSEMBLE study divides participants into two groups. One group will receive the investigational COVID-19 vaccine and the other will receive a placebo. The main purposes of the study are to:

  1. Check whether the experimental vaccine is safe
  2. Learn more about any side effects that can be caused by the vaccine – whether mild, moderate or severe
  3. Ensure that the vaccine is effective to prevent or lessen the severity of COVID-19

J&J’s ENSEMBLE vaccine trials were recently paused temporarily. This was because one of the participants suffered from an “unexplained illness.” The trials were resumed shortly after no clear cause was identified. The company has found no evidence that the vaccine candidate caused the adverse event.

The world awaits results from Phase 2 and Phase 3 clinical trials. J&J expects to know whether the vaccine works as early as December, and hopes to circulate their vaccine in the first quarter of 2021. However, much like the other COVID-19 vaccines in development, this is all tentative and not set in stone.

This post was written by Nidhi Parekh of The Shared Microscope. Check out The Shared Microscope on Twitter, hop over to their Facebook, or visit their Instagram for more fun and informative illustrations of biology concepts.

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