No 19/21 - 2021

Vaccination against COVID-19 - COVID-19 Vaccine Janssen^®

On 11 March 2021, the fourth vaccine against COVID-19 was authorised by the EU Commission following the recommendation of the European Medicines Agency (EMA). The vaccine was developed by the Belgian company Janssen, a subsidiary of the American company Johnson & Johnson and is marketed as COVID-19 Vaccine Janssen^®.

Due to US reports of rare but serious cases of blood clots, low platelet counts (thrombocytopenia) and in some cases haemorrhage, the US health authorities on 12 April decided to pause the use of COVID-19 Vaccine Janssen^®. Simultaneously, Janssen decided to pause vaccine supply to the EU, while the European Medicines Agency (EMA) studied this safety signal.

The rare but serious adverse effects observed following COVID-19 Vaccine Janssen^® have, by the EMA and the US Food & Drug Administration (FDA) alike, been found to probably be associated with COVID-19 Vaccine Janssen^®. It was also assessed that the adverse effects are triggered by the same mechanism as the rare but serious adverse effects previously observed following COVID-19 Vaccine AstraZeneca® (Vaxzevria^®) in several European countries, including Denmark. The adverse effects which have been coined VITT (Vaccine-Induced Immune Thrombotic

Thrombocytopenia) caused the Danish Health Authority to discontinue the use of Vaxzevria^® in the general vaccination programme as early as 14 April after consulting with a group of medical experts.

On 3 May, the Danish Health Authority decided that in the current Danish context, the benefit of COVID-19 Vaccine Janssen^® does not outweigh the possible risk of VITT following vaccination, and therefore it will not currently form part of the general COVID-19 vaccination programme .

Subsequently, a political decision was made to introduce an additional optional scheme through which the two EMA-authorised vaccines that the Danish Health Authority cannot generally recommend may be offered to persons who would also be comprised by the general vaccination programme, but who - following medical counselling and informed consent - want to become vaccinated with one of the two vaccines of the optional scheme. The legal and medical framework of this are described in further detail in Executive Order on Free Vaccination against COVID-19, no. 928 of 19 May 2021 (in Danish language), and in Guideline on Vaccination against COVID-19, no. 9352 of 19 May 2021 (in Danish language). The optional scheme came into force on 20 May 2021.

Furthermore, the Danish Health Authority has described the framework for the optional vaccine scheme that is not comprised by the general COVID-19 vaccination programme in the monthly publication Rationel Farmakoterapi (in Danish language). In addition to COVID-19 Vaccine Janssen® , the optional scheme also covers Vaxzevria^®.

About the COVID-19 Vaccine Janssen^®

The COVID-19 Vaccine Janssen® is currently the only EU-authorised vaccine to be administered in a 1-dose scheme. The EU Commission has authorised COVID-19 Vaccine Janssen® for everyone aged 18 years or more.

In line with the other authorised COVID-19 vaccines, the COVID-19 Vaccine Janssen® has been granted a conditional marketing authorisation in the EU. This means that Janssen is required continuously to report collected data to the EMA, and that the vaccine is monitored just like the Comirnaty^® vaccine, the COVID-19 Vaccine Moderna^® and Vaxzevria^®. Read more about this topic in EPI-NEWS 51/52b 2020. To achieve a standard marketing authorisation, the manufacturer must continuously report data from the clinical phase-3 trial. A description of the post-marketing studies that the manufacturer has an obligation to complete is provided in the so-called risk-management plan.

Information about the basis for the authorisation, product information, patient information leaflets, etc. are available at the website of the Danish Medicines Agency (in Danish language).
COVID-19 vaccine Janssen^® is based on a known vaccine technology and employs an adenovirus vector (Ad.26.COV2-S) that enhances the immune response. The vector is a non-replicating adenovirus containing the genetic code for the spike gene located on the surface of new corona virus (SARS-CoV-2). The vector is absorbed by the cells where it releases the coding DNA into the nucleus of the cell and mRNA is produced, which is then transported out of the cell core and translated to spike protein. The protein and protein fragments are subsequently presented on the surface of the cell and will therefore activate the immune system of the vaccinee, thereby inducing the production of protective antibodies and releasing a specific cellular (T-cell mediated) immune response.

Efficacy of the vaccine

COVID-19 Vaccine Janssen^® was tested in an ongoing randomised, double-blind, placebo-controlled phase-3 multicenter trial conducted in the US, South Africa and Latin America, to assess the efficacy, safety and immunogenicity of a single dose of COVID-19 Vaccine Janssen^® for prevention of COVID-19 in adults aged 18 years or more.

A total of 44,325 persons participated in the trial. 21,895 persons were given COVID-19 Vaccine Janssen^® and 21,888 were given a placebo. All participants were followed for 1-124 days (median: 58 days) after their vaccination.

For all age groups, 14 days after vaccination a total of 116 laboratory-confirmed COVID-19 cases occurred in the vaccine group (n = 19,630) and 348 in the control group (n = 19,691). This corresponds to a 66.9% (95% confidence interval 59.0%-73.4%) vaccine efficacy. From this group, 14 of the laboratory-confirmed COVID-19 cases were severely affected in the vaccine group and 60 of the laboratory-confirmed COVID-19 cases were severely affected in the control group. This corresponds to a 76.7% (95% confidence interval 54.5%-89.1%) vaccine efficacy against severe COVID-19 illness.

Overall, the efficacy was comparable for younger and older trial participants, here stated at 14 days after vaccination:

• for the group of 18-64-year-olds, the vaccine efficacy was 64.2% (95% confidence interval 55.3-71.6).
• for the group aged 65-years or more, the vaccine efficacy was 82.4% (95% confidence interval 63.9-92.4).
• for the group aged 75-years, the vaccine efficacy was 100% (95% confidence interval 45.9-100.0).

Furthermore, the effect was comparable in persons with and without comorbidity (a minimum of one concurrent condition). When vaccination efficacy was stated based exclusively on severe COVID-19 cases, a total of 14 cases were observed 14 days after vaccination in the group of 19,630 who were given COVID-19 Vaccine Janssen®, and 60 cases were observed among the 19,691 persons who were given placebo, corresponding to a 76.7% (95% confidence interval 54.6%-89.1%) efficacy.

Who may receive the vaccine?

Persons aged 18 years or more to achieve active protection against SARS-CoV-2. No dose adjustment is used in elderly people (> 65 years).

Side effects

The most frequent side effects were pain at the infection site (48.6%), headache (38.9%), fatigue (38.2%), muscle soreness (33.2%) and nausea (14.2%). Fever (defined as a temperature > 38.0°C) was observed in 9% of the participants.

Most side effects occurred within one to two days after vaccination, were mild to moderate and lasted 1-2 days. These side effects occurred in more than one in every ten persons.
Possible serious side effects were reported among 0.4% of all study participants (a total of 83/21,895 who received COVID-19 Vaccine Janssen^®, and a total of 96/21,888 who received a placebo).

Special precautions and attention points

For a description of thrombosis with thrombocytopenia (VITT), please see the summary of product characteristics.

All vaccinations carry a small risk of a strong allergic reaction (anaphylaxis).Anaphylaxis preparedness measures must be in place at all vaccination sites, and it falls upon the physician responsible for the vaccination to ensure this. Observation is recommended for a minimum of 15 minutes and optionally longer as deemed necessary by a physician.
Hypersensitivity to any of the vaccine’s ingredients or excipients.

Vaccination should be postponed in case of acute illness and fever > 38.0°C.

Persons who have experienced an immediate anaphylactic reaction after receiving other vaccinations or after having another medicinal product injected should be assessed by a physician before being vaccinated with COVID-19 vaccines as they may be at increased risk of experiencing an allergic reaction. These patients may be assessed by their GP, who may confer with a specialised allergy centre as needed. Particular attention should be given to persons who may have an undiagnosed allergy to the ingredient polyethylene glycol (PEG). COVID-19 Vaccine Janssen^® does not contain PEG but does contain polysorbate 80, and cross-allergenicity has been observed for these two substances.

Patients with severe or moderate haemophilia A or B or severe von Willebrand’s disease may be vaccinated intramuscularly if they have received prophylactic treatment with a factor product a few hours before their vaccination. Patients with milder haemophilia must contact their haemophilia centre to establish if they should receive prophylactic haemophilia medicine before being vaccinated.

Standard anticoagulative (AC) treatment is not normally a contraindication to intramuscular injection and is therefore also not a contraindication to vaccination.

The efficacy of the vaccine may be reduced in persons with a reduced immune response, including people who are receiving immunosuppressive treatment.

Various Danish medical societies have published medical recommendations for vaccination of their patient groups. Please note that the recommendations may have been updated since the latest version of the Danish Health Authority’s guideline on the handling of COVID-19 Vaccination was published on 20 May 2021.

Clinical protection against SARS-CoV-2 cannot be guaranteed in all vaccinated persons, cf. the above section on the efficacy of the vaccine.

Pregnancy and breast-feeding

Experience with use of COVID-19 Vaccine Janssen^® in pregnant women is limited. Animal trials with COVID-19 Vaccine Janssen^® indicate no direct or indirect harmful effects on pregnancy. Even so, the administration of COVID-19 Vaccine Janssen^® should be considered in pregnant women only if the potential benefits outweigh the potential risks for the mother and foetus.

Due to lacking safety data, the vaccine should not be given to pregnant women, and pregnancy should be excluded through pregnancy work-up before vaccinating women of fertile age. In case of amenorrhoea, the woman should be encouraged to take a pregnancy test before proceeding to vaccination, if relevant. If a woman has a non-acknowledged pregnancy at the time of her vaccination, termination of pregnancy is not recommended as the vaccine is not a live attenuated vaccine why no or only very limited foetal harm is expected.

It remains unknown if COVID-19 Vaccine Janssen^® is excreted in breast milk. Even so, the administration of COVID-19 Vaccine Janssen^® should be considered in breast-feeding women only if the potential benefits outweigh the potential risks for the mother and child.

The vaccine is not expected to affect the fertility of either men or women. Animal studies have shown no vaccine-related effects on female fertility or pregnancy.

Dispensing

So far, COVID-19 Vaccine Janssen^® is limited and will be supplied to the stakeholders who form part of the optional vaccination scheme. At the SSI, the vaccine is stored in freezing (-25 to -15°C) and will be provided frozen until further notice.

The vaccine is provided in packages containing 10 or 20 multidose vials per pack. Each vial contains a minimum of five 0.5 mL doses.

Storage and handling

Unopened vials have a shelf life of two years, stored at -25 °C to -15 °C.

Thawed unopened vaccine has a shelf life of up to three months at 2-8 °C.

Once the vial has been opened, the vaccine remains usable for six hours at 2-8 °C or at room temperature (up to 25 °C) for up to three hours. Once drawn into the syringe, the vaccine remains usable for up to 3 hours at room temperature according to the manufacturer’s data. Vaccines that have not been used within the stated time periods must be discarded.

Store in the original package to protect from light. Thawed vaccine must not be re-frozen.

Preparation

The vaccine is supplied ready for use in vials containing 3.1 mL suspension. Use aseptic technique when preparing the vaccine. Inspect the vaccine before drawing it from the vial. The solution must appear as a colourless to yellowish, clear to very opalescent suspension. Discard this medicine if you notice particles in the solution or if the solution is discoloured. Gently swirl the vial for ten seconds while holding it upright. 0.5 mL of vaccine is withdrawn into the syringe and injected intramuscularly. Changing the needle between withdrawal from the vial and injection is unnecessary. The SSI has prepared an infographic (in Danish language).

According to the EMA summary of product characteristics , the vial will provide a minimum of five 0.5 mL vaccine doses, and any unused diluted vaccine is discarded as usual and no more than six hours after its preparation. If any full 0.5 ml vaccine doses remain after the doses have been drawn, these may be drawn and used. Mixing left over vaccines from various vials with COVID-19 Vaccine Janssen^® to reach a full dose is not allowed.

Dosage and administration

COVID-19 Vaccine Janssen^® is a ready-to-use multidose vial that should not be diluted. Each vial contains 3.1 ml, equivalent to a minimum of five 0.5 mL doses. Each vaccine dose contains 8.92x1010 infectious units.

A single 0.5 mL dose of undiluted vaccine is given.

Immunisation is done by intramuscular injection into the deltoid muscle. In case of contraindications to vaccination in the deltoid muscle, the vaccine may be administered to the central section of the lateral great muscle (the thigh muscle). Based on a precautionary principle, we recommend aspiration before injection.

Registration

All COVID-19 vaccines must be registered in the Danish Vaccination Register (DVR), either by rapid or standard registration, see registration instructions here (in Danish language). We encourage that the vaccination is registered as quickly as possible after the time of the vaccination. To ensure quality in the monitoring of the vaccines, it is important to ensure correct registration of product name and batch/lot number.

Information for the person receiving the vaccination

The person receiving the vaccine should be given a folder. The folder provides information about the most frequently occurring side effects and informs you that you should see your doctor if you experience any serious side effects/symptoms after being vaccinated.

Phone advice is also available to the general public via the joint corona hotline of the Danish authorities at +45 7020 0233. Phone advice does not include advice about symptoms or medical assessments in relation to citizens; for these complaints, please refer to your general practitioner.

Additional vaccination to the person giving the vaccination

Vaccinators may find additional information about COVID-19 vaccination at the websites of the Danish Health Authority, the Danish Medicines Agency and Statens Serum Institut. At the website of the SSI, you can download vaccine-specific descriptions  and infographics about the vaccines.

The SSI has prepared a questions and answers page about COVID-19 vaccination at our COVID-19 subsite for use by healthcare workers (in Danish language). For further information, please see the Danish Health Authority’s Knowledge Bank for General Practitioners and Vaccinators.

If the need arises for vaccination-related advice, healthcare workers may contact the Department of Infectious Disease Epidemiology and Prevention. We are open for phone-based advice at +45 3268 3037 from Monday to Friday 8.30-11.00 a.m., except for Wednesdays 12.30-3.00 p.m. Beyond these periods, the department can be contacted during daytime office hours on phone +45 3268 3038. You may also write to covidinfo@ssi.dk. On working days, we aim to respond within the day the request was made, but we cannot guarantee that this is possible in all cases. Outside normal office hours, the physician on call may be contacted for acute advice on phone +45 4131 7404.

(S.B. Asmussen, L.K. Knudsen, K. Finderup Nielsen, P.H. Andersen, P. Valentiner-Branth, Department of Infectious Disease Epidemiology and Prevention)