Covid-19 vaccine Ad26.CoV2S, marketed by the pharmaceutical company Janssen (part of the Johnson & Johnson group), received authorisation in the European Union on 11 March 2021. It is expected to become available in France in spring 2021. Covid-19 vaccine Ad26.CoV2S is a viral vector vaccine based on a different vector from the one used in covid-19 vaccine ChAdOx1-S, marketed by AstraZeneca (see > HERE and > HERE). What are the main data available as of mid-March 2021 from the clinical evaluation of covid-19 vaccine Ad26.CoV2S?

Human adenovirus as a viral vector. The vector of a viral vector vaccine is a non-pathogenic or mildly pathogenic virus that has been modified so that its genome contains a gene encoding a protein from the virus against which an immune response is to be mounted. Once injected, the viral vector enters the vaccinee’s cells, which then synthesise the proteins encoded by the modified viral genome, including the protein of the virus against which an immune response is sought (1).

The viral vector in covid-19 vaccine Ad26.CoV2-S is a human adenovirus of serotype 26 (Ad26) that has been modified at genomic level to block its replication and to insert the gene encoding the spike protein of the Sars-CoV-2 coronavirus (2,3). The aim is to elicit an immune response against the Sars-CoV-2 spike protein, which is also the aim of covid-19 vaccine ChAdOx1-S (by AstraZeneca) and the currently available messenger ribonucleic acid (mRNA) vaccines tozinameran (Comirnaty°, by Pfizer and BioNTech) and mRNA-1273 (by Moderna) (1). Like these three vaccines, covid-19 vaccine Ad26.CoV2-S contains no adjuvants (3).

The viral vector Ad26 is already in use in a vaccine against Ebola virus disease, Ebola vaccine Ad26.Zebov-GP (Zabdeno°), that was authorised in the European Union in 2020. A number of other vaccines based on this vector are currently under development (2). Only short-term data are available as yet on the use of this vector in humans.

A reduction of about two-thirds in the incidence of infection, from day 15 after a single injection. As of mid-March 2021, covid19 vaccine Ad26.CoV2S has been evaluated in one double-blind randomised trial that compared a single intramuscular injection of this vaccine versus placebo, in about 40 000 adults (2). The trial was conducted in the United States, Latin America and South Africa from September 2020. The trial participants had an average age of 51 years. 20% of them were aged 65 years or older, and only 4% (about 1500 participants) were 75 or older (4). 41% of the participants had at least one risk factor for developing severe covid-19 other than their age (mainly obesity or hypertension) (2).

One of the primary endpoints was symptomatic, laboratory-confirmed covid-19 from day 15 onwards after the injection (2). The results available in mid-March 2021 are from an analysis performed in late January 2021, after a median follow-up of 8 weeks. 116 cases of covid-19 had been reported in the vaccine group, versus 348 in the placebo group, i.e. the vaccine reduced the risk of developing covid-19 by 67% (95% confidence interval (95CI) 59-73%). The vaccine appeared to have similar efficacy in participants with a risk factor for developing a severe form of covid-19. The vaccine’s preventive effect appeared to start 2 to 3 weeks after injection (2).

Reduced incidence of severe forms too. From day 15 after vaccination, 14 cases of severe covid-19 occurred in the vaccine group, versus 60 in the placebo group, i.e. the vaccine reduced the risk of severe covid-19 by about 77% (95CI 55-89%). Two participants were hospitalised for covid-19 in the vaccine group, versus eight in the placebo group. All of the 7 covid-19-related deaths occurred in the placebo group (2).

Unknowns after the age of 75 years. Only 4% of the trial participants were aged 75 years or older. The number of cases of covid-19 in this subgroup (one in the vaccine group and nine in the placebo group) was insufficient to determine the efficacy of covid-19 vaccine Ad26.CoV2S in this age group (2). However, based on these results and those of epidemiological studies of other, already widely used, covid-19 vaccines, some degree of efficacy in older adults is likely (5).

Some efficacy against the South African variant. About 5000 trial participants were living in South Africa (2). In this subgroup, the risk of developing symptomatic covid-19 was 52% lower (95CI 30-67%) in those who had received covid-19 vaccine Ad26.CoV2S. The broad 95CI reflects the uncertainty surrounding this result. Sequencing of Sars-CoV-2 RNA performed during the trial showed that almost all of the participants who developed symptomatic covid-19 in South Africa were infected with the South African variant 20H/501Y.V2 (2).

It is not known, as of mid-March 2021, whether covid-19 vaccine Ad26.CoV2S is effective against infection with the UK variant 20I/501Y.V1 or the Brazilian variant 20J/501Y.V3.

Is one dose sufficient? The duration of protection after a single dose of covid-19 vaccine Ad26.CoV2S was not yet known in early March 2021 (3,4). Neither is it known whether a single dose is the best way of administering this vaccine. A trial to evaluate the efficacy of two doses, 56 days apart, is currently in progress in about 30 000 adults (2,4). The first results are not expected until early May 2021 at the earliest (3).

Frequent local and systemic reactions. The foreseeable adverse effects of covid-19 vaccine Ad26.CoV2S are those shared by most vaccines, in particular local reactions and systemic reactions (fever, headache, chills, etc.). Viral vector vaccines can also cause infection, especially in immunocompromised individuals (1).
 
In the clinical trial described above, about 6700 participants were investigated systematically in the days following vaccination for the presence of certain local and systemic reactions (2). About 50% of participants in the vaccine group experienced local reactions (pain, erythema, swelling), versus 19% in the placebo group. And 55% of participants in the vaccine group experienced systemic reactions (fatigue, headaches, muscle pain, nausea, fever), versus 35% in the placebo group. In the vaccine group, local and systemic reactions were more common in participants under the age of 60. In half of cases, local or systemic reactions lasted no more than 2 to 3 days. In rare cases, they persisted for more than 7 days (2).

Deep vein thrombosis was reported in 6 participants in the vaccine group, versus 2 in the placebo group. Pulmonary embolism occurred in 4 participants in the vaccine group, versus 1 in the placebo group (2). According to the US Food and Drug Administration (FDA), insufficient data are  available to establish a link between covid-19 vaccine Ad26.CoV2S and an increased risk of venous thrombosis. The FDA and the European Medicines Agency (EMA) nevertheless recommend close monitoring of these adverse events when this vaccine is deployed on a large scale (2,6).

Adverse events suggestive of an allergic reaction were slightly more common in the vaccine group, in particular rash (reported in 35 participants in the vaccine group versus 23 in the placebo group), urticaria (8 versus 5) or hypersensitivity reactions (9 versus 6), and asthma (7 cases versus 1) (3,6). No anaphylactic reactions were reported during the trial, but one case was reported outside the trial (2,3).

Three patients developed facial paralysis in the vaccine group, versus 2 in the placebo group. One case of Guillain-Barré syndrome occurred in each group (6).

According to the data presented by the FDA in late February 2021, 5 deaths occurred in the vaccine group (all from a cause other than covid-19), versus 20 in the placebo group (7 from covid-19 and 13 from another cause) (2).

Multidose vials, storage in a refrigerator. Each vial of covid-19 vaccine Ad26.CoV2S contains 5 doses, each dose consisting of 0.5 ml of suspension. The instructions in the summary of product characteristics (SPC) include: “Before administering a dose of vaccine, swirl the vial gently in an upright position for 10 seconds. Do not shake”. The vials are to be stored in a freezer between -25°C and -15°C for 2 years at most, or in a refrigerator between 2°C and 8°C for 3 months at most (3). Unopened vials can be stored without refrigeration for 12 hours at a maximum temperature of 25°C (2). Once a vial has been punctured, its contents must be used within 3 hours if kept at room temperature or within 6 hours if refrigerated (3).

In practice, a few points of reference. While awaiting a thorough analysis and more data, the main clinical evaluation data available in mid-March 2021 on covid-19 vaccine Ad26.CoV2S (marketed by Janssen of the Johnson & Johnson group) can be summarised as follows:

• This vaccine was primarily evaluated in a randomised clinical trial in about 40 000 adults that started in September 2020. The data available publicly date from late January 2021, after short-term follow-up (less than 8 weeks for half of the trial participants);
• The participants in this trial received a single intramuscular injection of the vaccine or placebo. The incidence of covid-19 was about 67% lower in the vaccine group. The incidence of severe forms of covid-19 was also lower in the vaccine group;
• About 1500 participants in this trial were aged 75 years or older, too few to determine the efficacy of the vaccine in this age group, although some degree of efficacy is likely;
• It is not yet known as of mid-March 2021 whether it would be useful to give one or more additional doses. A trial to evaluate two doses, 56 days apart, is in progress;
• The known adverse effects of covid-19 vaccine Ad26.CoV2S are mainly local and systemic reactions, affecting a high proportion of recipients of this vaccine;
• As with any new drug, the lack of long-term data means that much remains unknown about this vaccine.

In summary, as of mid-March 2021, covid-19 vaccine Ad26.CoV2S is another option to add to the covid-19 vaccines already available, and to the other preventive measures, including distancing and hygiene rules, which should still be implemented, even by vaccinees.

©Prescrire 23 March 2021

Sources:

1. Prescrire Editorial Staff "The ChAdOx1 nCoV-19 covid-19 vaccine from AstraZeneca: great uncertainty over its efficacy" 29 January 2021. > HERE
2. US FDA "FDA Briefing document for vaccines and related biological products advisory committee meeting. Janssen Ad26.CoV2.S vaccine for prevention of covid-19" 26 February 2021.
3. HAS "Stratégie de vaccination contre la covid-19. Place du vaccin covid-19 Janssen" 12 March 2021.
4. Janssen Biotech "Covid-19 vaccine Ad26.CoV2.S. Sponsor briefing document for vaccines and related biological products advisory committee” 26 February 2021.
5. Prescrire Editorial Staff "The AstraZeneca covid-19 vaccine: British epidemiological data on the vaccination of older adults, and reassuring pharmacovigilance data" 15 March 2021. > HERE
6. EMA - CHMP "Public assessment report for Covid-19 Vaccine Janssen. EMEA/H/C/005737/0000" 11 March 2021.
    

For more information:

• "Covid-19: Follow Prescrire's independent, evidence-based analysis of the pandemic" > HERE