ADENOVIRUS-BASED VACCINES FOR COVID-19

Adenoviruses have been used in gene therapy and have also been researched for use in vaccines for decades. Two adenovirus-based vaccines have been authorised for emergency use to fight COVID-19 in the European Union, along with two mRNA vaccines.

Learn more about how the adenovirus-based vaccines work and find answers to many common questions below.

What is COVID-19?

COVID-19 is an infectious disease caused by a strain of coronavirus discovered in 2019, called SARS CoV-2. The disease is typically spread through respiratory droplets in the air from an infected person. SARS CoV-2 causes a range from no symptoms (asymptomatic) to severe symptoms, including fever, cough, fatigue, and breathing difficulty. Coronaviruses are a family of viruses that cause a number of different diseases, including COVID-19.

The COVID-19 outbreak is defined as a pandemic, because it has spread across multiple countries and has affected a large number of people.

What are adenoviruses?

Adenoviruses are a group of viruses that cause common illnesses and symptoms, like fevers and coughs. Scientists have learned how to disable the genes that can cause illness while keeping the ability to get into cells to treat or prevent disease. This means that the engineered “virus” used in the vaccine cannot replicate, or make copies, in the human body to cause illness.

How does an adenovirus-based vaccine work against COVID-19?

An adenovirus can be used as a vector, or carrier, to deliver a gene to cells with instructions to make a protein that is required for the body to function properly. You can think of the adenovirus vector as an envelope with a message inside. In the case of a vaccine to fight COVID-19, the message being delivered is a gene that will instruct cells to temporarily make just enough of the SARS-CoV-2 spike protein to activate the immune system. The cells are not given enough instructions to build the full virus so the vaccine cannot cause COVID-19. This spike protein is an antigen that is recognised by the immune system as a foreign invader. The antigens trigger the immune system to produce specific protective antibodies that neutralise the virus – in this case, the antibodies needed to fight COVID-19.

If a person is exposed to SARS-CoV-2 after receiving the vaccine, the immune system will detect the familiar antigens and produce antibodies to attack them. A vaccinated person’s immune system can better defend against the infection, eliminating it altogether or greatly reducing the severity of the infection.

How many doses are required?

The AstraZeneca/Oxford University vaccine (Vaxzevria) is given as two injections. The second dose should be given between 4 and 12 weeks after the first dose.

The Janssen adenovirus-based vaccine for COVID-19 was authorised to be given in a single dose. There is another clinical trial under way to test the effects of two doses, but the results of the trial are still awaited.

What are clinical trials?

Clinical trials are required research processes that study the way an intervention interacts with the body. Clinical trials typically take many years and are divided into different phases that answer specific questions about the treatment, primarily whether it is safe and effective. However, the EMA and the European National Competent Authorities (NCAs) have created expedited pathways and programmes to accelerate the process while still maintaining the same high standards. This is typically done for medicines and therapies for serious diseases with no other treatment options, or for public health emergencies such as interventions that fight COVID-19.

Do I still need to get vaccinated if I already had COVID-19?

Yes. The European Centre for Disease Prevention and Control (ECDC) recommends being vaccinated even if you have already had COVID-19, because you can get infected more than once. You may have short-term antibodies for protection after recovering from COVID-19, but we don’t know for how long this protection will last. In addition, there were no concerns reported from the clinical trials if a participant had COVID-19 and was also vaccinated.

Are there certain people who should not receive the vaccine?

Very few, but individuals with known history of a severe allergic reaction (e.g. anaphylaxis) to any component of the COVID-19 vaccines should not receive the vaccine. In addition, consider speaking with your doctor to make the decision if:

You are immunocompromised, meaning you have a known impaired immune system
You are pregnant or breastfeeding
You have a history of severe allergic reaction such as anaphylaxis to any vaccine or injectable therapy
You are currently a participant in a gene therapy clinical trial

These vaccines are currently not being given to children under the age of 18, but with more paediatric clinical trial data, they may eventually be available to younger ages.

If I have a rare disease, will an adenovirus-based vaccine affect my eligibility to receive gene therapy in the future?

Speak with your healthcare team to consider carefully if an adenovirus-based vaccine is right for you. Gene therapy treatments often use a viral vector to deliver a working gene. However, there is concern that being exposed to a specific virus could build natural immunity and therefore would make treatment using a similar viral vector ineffective.

If I am currently a participant in a gene therapy clinical trial, can I get the vaccine?

Check with the provider of the gene therapy trial before receiving a vaccine.

The adenoviral vector enters the cell to trigger an immune response to build antibodies.

How effective are the adenovirus-based vaccines?

Vaxzevria (Astra Zeneca) offers a good level of protection against COVID-19 – a critical need in the current pandemic. The main trial showed that the vaccine has around 60% efficacy and most side effects are mild to moderate and are gone within a few days.

Further trials and additional studies are ongoing and will provide information on how long protection lasts, including against new variants of the virus, how well the vaccine prevents severe COVID-19, how well it protects older people, immunocompromised people, children and pregnant women and whether it prevents asymptomatic cases.

The Janssen clinical trials for the adenovirus-based vaccine also had good results. The clinical trials data are from 43,783 participants in the U.S.A., South Africa, certain countries in South America and Mexico, who did not have evidence of SARS-CoV-2 infection prior to receiving the vaccine. Of the 21,895 participants that received the vaccine, it was found to be 66% effective at preventing moderate to severe COVID-19 from occurring at least 28 days after vaccination. The vaccine was able to reduce the risk of adults getting severe or critical disease by 85% and offered complete protection against COVID-related hospitalisations and deaths.

At this time, data is not available to determine for how long the vaccines will provide protection. However, having protection for any length of time from vaccination would be beneficial compared with having no protection. Being vaccinated may also protect people around you, particularly people at increased risk of severe illness from COVID-19.

Independent studies of COVID-19 vaccines coordinated by EU authorities will give more information on the vaccine’s long-term safety and benefits in the general population.

Are there any side effects of these vaccines?

Like any medical intervention, vaccines can cause side effects, which are potential effects known to be caused by a certain vaccine, based on studies. Side effects are a type of adverse event. An adverse event is any health problem ranging from minor to serious, that happens after vaccination, whether it is caused by the vaccine or not.

During testing of the Janssen adenovirus-based vaccine in clinical trials the participants that received the vaccine were followed for about eight weeks after vaccination. The most reported side effects were pain at the injection site, headache, fatigue, muscle aches and nausea. Most of these side effects were mild to moderate in severity and lasted 1-2 days. This often means that your immune system is doing its job.

The most common side effects with Vaxzevria in the trials were usually mild or moderate and got better within a few days after vaccination. The most common side effects are pain and tenderness at the injection site, headache, tiredness, muscle pain, general feeling of being unwell, chills, fever, joint pain and nausea. They affected more than 1 in 10 people.

Thrombocytopenia (low levels of blood platelets), vomiting, diarrhoea, swelling and redness at the injection site occurred in less than 1 in 10 people. Lymphadenopathy (enlarged lymph nodes), decreased appetite, dizziness, sleepiness, sweating, abdominal (belly) pain, itching and rash occurred in less than 1 in 100 people. Thrombosis (formation of blood clots in the blood vessels) in combination with thrombocytopenia occurred in less than 1 in 10,000 people. Allergic reactions have occurred in people receiving the vaccine, including some cases of severe allergic reactions (anaphylaxis).

As for all vaccines, the COVID-19 Janssen and Vaxzevria vaccines should be given under close supervision with appropriate medical treatment available. Though unlikely, if you have any symptoms that concern you after you are vaccinated, call your doctor.

Will the vaccine stop me from spreading the virus to others?

At this time, there is no evidence for whether the vaccines prevent transmission of SARS-CoV-2 from person to person. Clinical trial data show that these adenovirus-based vaccines do a very good job at preventing symptomatic COVID-19, but data is still being collected to understand how well the vaccine prevents asymptomatic infection (infection without symptoms). Research is ongoing to determine whether a vaccinated person might still be able to transmit SARS-CoV-2 to someone else who is not vaccinated. This is why it is important for a large proportion of the population to be vaccinated.

Will the vaccine change my DNA?

No, the adenovirus-based vector used for the vaccines is non-integrating. That means the DNA (or gene) they carry won’t insert itself into the cell’s genome. So, if the viral vector is taken up by a cell that divides, the gene won’t be copied with each cell division and will be lost over time. The adenoviral vector carrying the gene is only in the body long enough to do its job of building antibodies, will eventually be cleared out, and won’t change a person’s DNA.

How does a vaccine help build herd immunity?

Vaccinations and herd immunity are not two separate approaches to fighting a pandemic. Herd immunity occurs when a large portion of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely. Vaccines are used to help populations reach herd immunity faster and without spreading illness. Advancements in vaccines are some of the greatest public health achievements over the last century. The only way we can build enough protection against the virus in our communities is if the majority of people receive the vaccine.

How were the adenovirus-based vaccines produced and tested so quickly?

The vaccines for COVID-19 have been developed at a record-setting speed, but they were still thoroughly tested to meet rigorous safety and efficacy standards. Before it is made widely available, any vaccine needs to be first studied in clinical trials and it is reviewed by an agency that oversees the safety and effectiveness of medical products. In Europe, this is done by the European Medicines Agency (EMA).

Starting a clinical trial for any medical intervention requires a research team, adequate funding and resources, and enough initial patients and data to properly plan the study. It’s a daunting task and is often why research and development take so long. Because this disease is a global health emergency, funding has been quickly directed toward reducing many of these barriers. The goal is to treat this dangerous disease as soon as possible, and as SARS-CoV-2 infection rates increased in 2020, researchers were able to accumulate a wealth of data and eager volunteers for clinical trials. In addition, under the exceptional circumstances of the pandemic, a “rolling review” process has been applied to review drugs intended to prevent or treat COVID-19.

A rolling review is a regulatory tool that EMA uses to speed up the assessment of a promising medicine during a public health emergency. Normally, all data on a medicine or vaccine’s effectiveness, safety and quality and all required documents must be ready at the start of the evaluation in a formal application for marketing authorisation. In the case of a rolling review, EMA’s human medicines committee (CHMP) reviews data as they become available from ongoing studies. Once the CHMP decides that sufficient data are available, the company can submit a formal application. By reviewing the data as they become available, the CHMP can come to an opinion on the medicine’s authorisation sooner.

During the rolling review, and throughout the pandemic, EMA and its scientific committees are supported by the COVID-19 EMA pandemic task force (COVID-ETF). This group brings together experts from across the European medicines regulatory network to advise on the development, authorisation and safety monitoring of medicines and vaccines for COVID-19 and facilitate quick and coordinated regulatory action.

How do the vaccines currently authorised for emergency use compare?

In Europe, there are currently four different COVID-19 vaccines that have received emergency use authorisation: two mRNA-based vaccines – Pfizer/BioNTech (also known as Comirnaty) and Moderna – and two adenovirus-based vaccines – AstraZeneca/Oxford University (Vaxzervria) and Janssen.

More vaccines authorised for emergency use means more people can get vaccinated sooner. The adenovirus-based vaccines do not need to be kept as cold as the mRNA vaccines, which makes them easier to distribute, while the mRNA vaccines are easier to make compared to the adenovirus-based vaccines, which need a viral vector to deliver genes to the cells.

All the vaccines provide protection against COVID-related hospitalisations and deaths.

Where can I find additional information?

The European Centre for Disease Prevention and Control (ECDC), the European Medicines Agency (EMA) and the World Health Organization (WHO) offer credible resources about COVID-19 and vaccines for COVID-19.

Last updated: 10 May 2021

This content was adapted from the American Society of Gene and Cell Therapy Patient Information Programme (https://patienteducation.asgct.org/)