The journey to
the COVID-19 vaccine

All of us are impacted. Hoping for the vaccine. Now it is here. Never before in history a vaccine has been developed faster.

“The production of the vaccine had already begun despite the financial risks involved, to make sure it would be available as soon as possible.”

Johan Van Hoof, Global Head Infectious Diseases & Vaccines, Janssen R&D

“The crisis in the world is so big that each of us will have to take maximum risk now to put this disease to a stop.”

Paul Stoffels, Chief Scientific Officer and Vice Chairman of the Executive Committee Johnson & Johnson

The Race

 

All eyes turned towards China in January 2020, as a stunned and anxious world followed the outbreak of the infectious disease caused by the COVID-19 virus in Wuhan. The scientists as well as Janssen, the pharmaceutical companies of Johnson & Johnsonsoon realised that this outbreak could lead to a global pandemic. Paul Stoffels, M.D., Janssen's Worldwide Chief Scientific Officer, responded immediately. Stoffels – a Belgian physician – is the driving force behind the 30-year fight to develop new vaccines against pathogens such as HIV, Zika, Ebola and RSV (respiratory syncytial virus) – and he was determined to defy this new and aggressive virus.

 

investment in vaccines

 

Initial discussions followed with Stoffels' colleague Johan Van Hoof, the Global Head of Vaccines at Janssen Vaccines. The two experts quickly concluded that “our research platforms and the scientific knowledge available to us” could be used to drive ahead the development of a potential emergency vaccine against COVID-19.

 

But how does the virus work? How does Corona affect the human body? You can learn more about this in this explanatory video.

At Janssens facility in Leiden, Netherlands, where vaccines are developed, the team of scientists was highly receptive to the proposals put forward by the two colleagues. The team headed by Hanneke Schuitemaker, Head of Viral Vaccine Discovery in Leiden, started work on designing the vaccine and structuring the first vectors “as soon as the genetic RNA sequence for SARS-CoV-2 was published on 10 January 2020.” These were challenging times for the experts at Janssen Vaccines. But the biologists, virologists, pharmacists, biochemists, biotechnologists, process engineers and medics – all of them specialists in their fields – had an ace up their sleeve because they were able to draw on the expertise and the extensive database they had built up in recent years: a vast reserve of know-how on vaccine technology as well as clinical safety and efficacy trials.

 

No compromises on safety

 

Dirk Redlich, Head Technical Development of Vaccines, Janssen R&D, recalls the mood back then: “We felt confident because we could rely on our AdVac® technology, and we also had existing production capacity – those were decisive factors that would enable us to play a key part in the fight against the virus.” Redlich also emphasises that no compromises are made in regards to safety aspects, despite the rapid pace of development: “Performing the development steps in parallel does not mean that we omit any of the tests.”

“Treatments save lives, but vaccines save populations”

Hanneke Schuitemaker, Vice President Viral Vaccines, Janssen R&D

“We have already used our AdVac® platform for the development of our Ebola vaccine and saw that this method stimulates different parts of the immune system and activates different protective mechanisms”

Head Technical Development of Vaccines, Janssen R&D

One crucial fact is that modern vaccines are structured differently than their first-generation counterparts. For a long time, only killed or attenuated living viruses were injected. But for some years now, the pharmaceutical industry has been building on genetic engineering as the basis for developing vaccines – an approach that uses decoding of the genetic code of the pathogen's DNA/RNA. This knowledge about selected genetic sequences of the pathogen's genetic material is also utilised in what is known as vector engineering – and Janssen is applying this method in its development work on the coronavirus vaccine.

 

Shuttle into human cells

 

Vector vaccine technology as such is not brand new: it is one of the many advances in genetic engineering that were developed in the 1990s. The technology currently used by Janssen for the coronavirus vaccine was invented by Crucell, a Dutch startup, and was then developed by Janssen until it was ready to market.In this context, scientists use the term “vector” to describe a virus that is harmless to humans, into which a partial sequence of the pathogen's genetic material is incorporated with the help of genetic engineering methods. The vector functions as a shuttle or taxi to transport fragments of the pathogen's genetic material to human cells. The human cell “reads out” this viral genetic information and goes on to produce its protein fragments, which the immune system recognises as foreign. The body is then able to build up protective immunity against this pathogen.

 

In this video you will learn how vaccines work:

Vector technology has now become established as a successful method. Janssen had good reason to celebrate on 1st July 2020, because the pharmaceutical company was granted European market authorisation for its first vector vaccine against Ebola. This breakthrough fills Dirk Redlich with optimism that the coronavirus vaccine can also be manufactured successfully on the same technology platform. “In the case of Ebola, we saw that the vector virus method stimulates various parts of the immune system and activates different protective mechanisms.” Additional candidate vaccines against RSV and HIV are already in the late phases of development.

On the way to Africa: shipping of Ebola vaccine.

Development of new vaccines such as these begins with decoding of the pathogen's genetic material so the researchers can identify the gene segments that are relevant for the immune response. These fragments of genetic material are incorporated into the adenovirus vector. To ensure that this intrinsically harmless common cold virus really is incapable of multiplying independently in human cells, the vector viruses are also modified so that their biotechnological replication is only possible by means of a specially modified cell line. This replication takes place in bioreactors with capacities of up to 900 liters. Billions of vector viruses are then extracted from the cultivated cells, purified and filled into ampoules under sterile conditions.

 

GENETICALLY ENGINEERED VECTOR VIRUSES

 

This highly complex process requires enormous knowledge. Two sites in the Janssen group – in Leiden and Bern – share the necessary expertise. The vector viruses are genetically engineered in the high-tech laboratories at the Discovery department in Leiden and then, according to requirements, they are transferred to the two pilot plants for biofermentation and purification. The vaccine can also be filled into vials under sterile conditions in Bern. After final packaging and labelling, it then embarks on the journey to Belgium, Brazil and the USA for the first phases of the clinical trials. On 23 September, Johnson & Johnson entered the third – and critical – phase of trials for its vaccine when it announced the initiation of the Phase 3 ENSEMBLE trial.

Bioreactor: the heart of controlled virus replication.

Sterile conditions: Filling line of the finished vaccine.

Hanneke Schuitemaker and all the workforce at Janssen Vaccines are fully aware that the pharmaceutical industry's commitment to producing a vaccine offers the only chance of vanquishing the pandemic at present. “Treatments save lives, but vaccines save whole populations” she points out. One thing is clear to this Dutch scientist who – together with the teams in Leiden and Bern – is devoting every effort to completing the development work in the shortest possible time: “People who get themselves vaccinated aren't just taking responsibility for themselves – they are also helping to make sure that the transmission chain ends with them, so they are keeping other people healthy.” Given the progress achieved thus far, the employees are in confident mood. And for his part, Paul Stoffels – who has fought to develop so many vaccines in the past – is convinced “that we will be able to produce a huge amount doses of vaccine in 2021.”

With heart and soul: the Janssen Vaccines team in Bern.

The last three steps before the goal is reached

It usually takes many years to develop a vaccine – but thanks to new technologies, the process will move far more swiftly for the vaccine against COVID-19.

These are the phases in the development of the COVID-19 vaccine at Janssen Vaccines:

1. January 2020: Johnson & Johnson announces that the company's pharmaceutical arm will collaborate with multiple global partners to combat the current COVID-19 pandemic by developing a vaccine. Once the genetic information from the SARS-CoV-2 virus has been decoded, the genetic sequences for the vector vaccine are determined in the Discovery Labs at Leiden (Netherlands); during spring, several apparently suitable candidates for a vaccine are identified. Viral constructs can only be used if they show maximum prospects of success in terms of safety as well as efficacy. Once the most effective candidate is selected, the vaccine is produced in larger quantities for the first time. The formulation of this vaccine concentrate is finalised in Bern at the end of June, followed by sterile filling into vials for the clinical trial phases.

2. From July 2020 onwards: start of clinical trials.
There are three successive phases of clinical trials:

Phase 1 trial: Safety and Tolerance

A small group of volunteers receive the candidate vaccine. The main goals in this phase are to assess whether the vaccine is safe, and to determine the type of immune response that is induced.

Phase 2 trial: Efficacy and dosage

A small group of volunteers receive the candidate vaccine. The main goals in this phase are to assess whether the vaccine is safe, and to determine the type of immune response that is induced.

Phase trial 3: efficacy, side effects (if any)

In this decisive phase, the goals are to provide broad-based substantiation for efficacy and to record side-effects (even if they are rare).

 

After the results from Phase 1/2a proved positive, the Phase 3 study of the COVID-19 vaccine was launched in September 2020 under the name ENSEMBLE. The goal of this study, which involved thousands to tens of thousands of volunteers, was to discover whether the candidate vaccine is safe and efficacious in comparison to a placebo.

 

A total of 43,783 people from various regions of the world took part in the study, including a certain percentage of participants aged over 65. The subjects also included a number of participants who were infected with a new variant of the virus.

 

The first interim protocol on the ENSEMBLE study was published on 29 January 2021. Overall, the Janssen COVID-19 vaccine candidate showed 66% effective protection against moderate to severe COVID-19 infection in the study after 28 days, with onset of the protective effect observed after as few as 14 days. 28 days after vaccination, the protection rates were 72% in the USA, 66% in Latin America and 57% in South Africa. The protective effect proved to be consistent across all ethnic groups and age groups (including adults aged over 60 [N= 13,610]), and also in respect of efficacy against newly emergent strains of the coronavirus including some highly infectious variants that are present in the USA, Latin America and South Africa.

 

Efficacy of protection against severe COVID-19 infections was 85% after 28 days for all adults aged 18 or more, and this percentage increased over time. No further relevant cases were reported among vaccinated participants after day 49.

 

28 days after vaccination, the Janssen COVID-19 vaccine candidate demonstrated complete protection against COVID-19-related hospitalisations and deaths. There was a significant reduction in the number of COVID-19 cases requiring medical interventions such as hospitalisation, admission to an ICU, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). 28 days after vaccination, no cases were reported where medical interventions of these types were necessary among study participants who had received the Janssen COVID-19 vaccine candidate.

 

To develop an additional level of safety, Janssen has initiated a further clinical study with 30,000 subjects in the same age groups: this is ENSEMBLE 2, a large-scale, multi-country Phase 3 study to test the efficacy of the coronavirus vaccine in a two-dose regimen. This additional test aims to ensure the safety of the vaccine for individuals with pre-existing conditions and those aged over 65. Johnson & Johnson expects the third clinical phase to be completed in 2021.

 

3. The time during the test phases was utilised to ramp up production in parallel at various manufacturing facilities throughout the world.

Once all the clinical trial phases have been completed, the authorisation bodies in the countries concerned must examine and approve the safety, efficacy and ethical aspects of the vaccine (as well as other factors) in order to issue market authorisation. The organisations that carry out these reviews are the Food and Drug Administration (FDA) in the USA, the European Medicines Agency (EMA) in the EU, and the Swiss Agency for Therapeutic Products (Swissmedic) in Switzerland. This phase usually takes a long time because the dossier must be fully completed before submission, with all the data on development and clinical aspects. But in this respect too, the procedure for developing the COVID-19 vaccine differs in many ways: all the parties involved are collaborating simultaneously to complete a fast-track authorisation process in response to the pandemic emergency, but with no compromises on safety and efficacy.

On 1 December, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) – and also Swissmedic – enabled a rolling review of the investigational single-dose Janssen COVID-19 vaccine candidate. This decision was based principally on positive non-clinical data showing that the vaccine candidate elicits a robust immune response as demonstrated by neutralizing antibodies.

For more information on this subject, check our Clinical Protocol

https://www.jnj.com/coronavirus/ COVID-19-phase-3-study-clinical-protocol

Efficacy is the decisive factor

 

Alongside safety, the efficacy of a vaccine is one of the key criteria that enable it to receive authorisation. Efficacy is determined by calculating the percentage of people tested in the third clinical phases who are protected against infection and progression of the disease. The video on the Vox online portal explains how these efficacy rates are obtained and how they should be interpreted.

A feat of strength

The production of the COVID-19 vaccine is a huge task

 

When, billions of people ask themselves, will we finally have the vaccine against COVID-19? While the wait continues, an unprecedented mobilization is taking place behind the scenes at Janssen, the pharmaceutical companies of Johnson & Johnson, amongst its vaccines team. The goal is to bring this vaccine from 2021 to millions of people.

 

A huge task for everyone involved, because the development of a vaccine is one thing, the production and distribution of the vaccine until it finds its way to the end user is another chapter in the story. This chapter is usually opened as soon as a new drug or vaccine has been approved, but with the COVID-19 vaccine everything is different. At the moment, the entire supply chain is being ramped up in parallel with the development of the vaccine and is investing to expand its global manufacturing capabilities.

Dapo Ajayi is one of the key people responsible for this at Janssen. The Vice President Vice President, Technical Operations & Supply Chain Strategy, Johnson & Johnson has been working with her team for months on the challenge of producing and delivering the vaccine in large quantities on different continents. To accomplish this, she says in the interview, is “a great example of how the technical side of the company and R&D work together”.

The Interview

 

Dapo Ajayi. Vice President, Technical Operations & Supply Chain Strategy, Johnson & Johnson

Strictest quality control: Laborary assistants at work.

Special transport: Janssen employees in the cold store.

Transport of vaccine vials: safety through a consistent cold chain.

It is not only a matter of increasing production capacities for the vaccine all around the world, but also of procuring the necessary materials, such as the glass for the vials or the closures. New production facilities have to be brought on-line and cooperation agreements with partner companies have to be signed. Last, but not least, it is also a matter of setting up a seamless supply chain for the vaccine. To ensure that the active ingredient remains stable, it is recommended to transport and store it at -20 degrees. It is then thawed in the vaccination centers and can be stored at two to eight degrees for up to three months. Dapo Ajayi speaks of a “rush for global expansion”. Johnson & Johnson can “draw on existing collaborations with our partners”, and further partnerships are being entered into.

 

The challenge is that no matter where production, storage and delivery takes place, the exact same high standards can be guaranteed. Partners are selected according to this requirement, “in terms of what we expect in terms of quality, safety and manufacturing standards” the Vice President says. The company spares no resource or effort in this process, because even before the vaccine is approved, the entire supply chain, i.e. production and distribution, must be in full working order, ready to execute flawlessly.

 

As soon as the COVID-19 vaccine is approved by the authorities, if deemed safe and effective, vaccination can be started by governments and health authorities. And the long wait will finally come to an end.

Next Chapter

 

130 Years of vaccine know-how

 

Janssen Vaccines in Bern is working at the forefront of the Corona vaccine. This has a long tradition; the company has been developing vaccines for 130 years.

 

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