Update on SAGE/WHO recommendations for the use of the Janssen COVID-19 vaccine

On 9 December 2021, WHO released updated interim recommendations by the Strategic Advisory Group of Experts on Immunization (SAGE) for use of the Janssen Ad26.COV2.S COVID-19 vaccine. Following is a summary of the updated recommendations.  

• Second dose: The most recent results from ongoing Phase 3 studies indicate that administration of two doses increases the efficacy of the Ad26.COV2.S vaccine in all clinical endpoints compared to a single dose. WHO notes that countries can choose to use this vaccine with a single-dose or two-dose immunization schedule, taking into account that many countries face severe vaccine supply constraints combined with a high disease burden. A single dose of the vaccine is effective and facilitates rapidly increasing vaccine coverage, which in turn will reduce the burden on health care systems. A single dose may also be a preferred option for vaccinating hard-to-reach populations.
  As vaccine supplies and accessibility improve, countries should consider offering a second dose, beginning with high-priority populations outlined in the WHO Prioritization Roadmap. WHO recommends an inter-dose interval of two to six months. The choice for the interval depends on the epidemiological situation and the needs of certain subpopulations.
• Interchangeability with other vaccines and platforms: When a second dose of the Ad26.COV2.S vaccine is given, use of the same vaccine is considered standard practice.
  However, WHO supports a flexible approach to vaccination schedules, taking into account current vaccine supply and other access considerations, along with the potential benefits and risks of the specific products being used. Evolving evidence suggests that heterologous COVID-19 vaccination schedules, using WHO Emergency Use Listing (EUL) vaccines from different platforms, may be more immunogenic and effective than homologous schedules, depending on the specific platforms and the order of the products used. Two clinical trials have demonstrated that a single dose of the Ad26.COV.S vaccine and a second dose of an mRNA vaccine (BNT162b2 or mRNA-1273) induce neutralizing antibody concentrations 4 to 22 times higher than a second dose of the Ad26.COV2.S vaccine (1,2). Ad26.COV.S also has the ability to boost antibody concentrations six months after a primary two-dose series of mRNA vaccine, with increases in antibody responses at week four following the boost comparable to a homologous third dose of mRNA vaccine, but with higher T cell responses (3). No major safety concerns have been identified regarding the use of Ad26.COV2.S in heterologous schedules, although the overall study size is limited.  

• Safety: As of 31 August 2021, an estimated 33.5 million doses of Ad26.COV2.S vaccine had been administered worldwide. Based on post-marketing safety surveillance, the following safety concerns were identified:
  • Guillain-Barré syndrome (GBS): The incidence of GBS is estimated at 4.15 per 100,000 people vaccinated, based on a 42-day risk window.
  • Thrombosis with thrombocytopenia syndrome (TTS): TTS was reported as approximately 2 cases per million doses administered. The majority of the cases were in people under 65 years of age (83%), with 55% of cases in women and 45% in men. The mean and median times to onset of the event were 16.5 days and 12 days, respectively.
  • Capillary leak syndrome (CLS): Very rare cases of CLS (0.21 per million doses administered) have been reported, some in persons with a prior history of CLS, and some with fatal outcomes. The mean and median times to onset of the event were 1.3 days and 1 day, respectively.
  • In countries with ongoing SARS-CoV-2 transmission, the benefit of vaccination with the Ad26.COV2.S vaccine in protecting against COVID-19 far outweighs the risks of TTS, GBS, and CLS. However, benefit– risk assessments may differ from country to country, and countries should consider their epidemiological situation, individual and population-level risks, availability of other vaccines, and alternate options for risk mitigation. The benefit–risk ratio is greatest in older age groups, as the risk of severe COVID-19 disease outcomes, including COVID-19-related thromboembolic events, increases with age.

• Pregnant and breastfeeding women: WHO recommends the use of the Ad26.COV2.S vaccine in pregnancy only if the benefits of vaccination outweigh the potential risks. WHO does not recommend pregnancy testing prior to vaccination. WHO also does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
  In the case of breastfeeding women, WHO recommends the use of this vaccine, and does not recommend discontinuing breastfeeding because of vaccination.
• Immunocompromised persons (ICPs): WHO recommends a second dose for moderately or severely immunocompromised ICPs aged 18 years and older one to three months after the first dose. The most appropriate time for the second dose should be discussed with the treating physician, and may vary depending on the epidemiological setting and the extent and timing of immune suppressive therapy. There are no data available to determine the need and timing of a third dose.
• Co-administration with inactivated influenza vaccines: It is acceptable to co-administer Ad26.COV2.S with an inactivated influenza vaccine. Different arms for injection should be used when both vaccines are delivered during the same visit.

For more information on this update, visit: https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccinesSAGE-recommendation-Ad26.COV2.S-2021.1. 

1. Sablerolles R. Immunogenicity and reactogenicity of booster vaccinations after Ad26.COV2.S priming. medRxiv. 2021. doi: https://doi.org/10.1101/2021.10.18.21264979
2. Atmar RL. Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report. MedRxiv. 2021. doi: https://doi.org/10.1101/2021.10.10.21264827
3. Tan CS. Ad26.COV2.S or BNT162b2 Boosting of BNT162b2. Vaccinated Individuals. MedRxiv. 2021. doi: https://www.medrxiv.org/content/10.1101/2021.12.02.21267198v1