What is known about immunity beyond 6 months following a fourth COVID-19 vaccination (2 initial doses plus first and second booster doses), and does the evidence suggest healthcare professionals would benefit from an additional booster dose?

30 Sep 2022

What the research says:

Booster vaccination programmes at or around 6 months after completing an initial course (2 doses) have been widely adopted. However, waning of effectiveness against symptomatic illness has been observed following booster vaccination (Fabiani et al 2022; PHE 2022). On this basis, several countries have now approved a second booster dose, initially for older people, those who are immunocompromised and those with certain comorbidities.

The emergence of the Omicron variant has prompted consideration of the longer term protection against severe COVID-19 disease (PHE 2022). Two initial doses plus a first booster dose of current vaccines demonstrates somewhat reduced effectiveness against hospitalization and death against the Omicron variant compared with that conferred against earlier variants:

  • ~80% effective against hospitalisation among those aged 18–64 years and ~90% among those aged >64 years) waning to almost ~50% and ~75%, respectively, from around 4 months post-first booster vaccination
  • ~93% effective against mortality declining only slightly to ~87% at 10 weeks post-first booster vaccination

Data from Israel suggests that, in the face of the Omicron variant, a second booster dose restores protection against severe COVID-19 illness in people aged ≥60 years and at-risk populations, with waning of effectiveness in the following 4–6 months (Bar-On et al 2022; Magen et al 2022). Data from the US have also demonstrated additional protection in people aged ≥50 following a second booster dose in the context of Omicron predominance (Link-Gelles et al 2022). Studies specifically among healthcare workers suggest that a second booster vaccination can reduce the breakthrough infection rate even when the Omicron variant is the predominant circulating variant (Cohen et al 2022).

In terms of the quality of the immune response conferred following booster vaccinations, emerging data suggests that, while still eliciting an antibody response (Munro et al 2022), the resultant antibodies are less effective against the Omicron variant in terms of preventing illness, but still effective at preventing hospitalization and death (Hein et al 2022). These data emphasise the need for ongoing variant-adapted vaccine development. Vaccines with specificity against both the original strains and the OMICRON variant are under regulatory review and have been approved in a number of countries including Canada (Government of Canada 2022), the UK (MHRA 2022) and the US (Pfizer 2022).

What this means for your clinical practice:

  • Continue to encourage patients at increased risk for more severe illness from SARS-CoV-2 infection to consider additional COVID-19 booster vaccinations according to National Guidelines.
  • Healthcare workers should continue to consider COVID-19 booster vaccinations with current vaccines as they become eligible.
  • Individuals at high risk for severe illness or death from COVID-19 should get their fourth dose of vaccine now if it has been more than 6 months since their last dose. Booster vaccination should not be delayed if an Omicron-directed vaccine is not yet available.

With grateful thanks to Dr Fiona Mosgrove (GP and Clinical Lead Grampian Respiratory Improvement Programme, Aberdeen, Scotland, UK) for and on behalf of the IPCRG practice driven answers review group.

Supporting references:

Bar-On Y, et al. Protection by a fourth dose of BNT162b2 against Omicron in Israel. NEJM 2022;386:1377–80. Available at: https://pubmed.ncbi.nlm.nih.gov/35297591/. Accessed August 2022.

Cohen MJ, et al. Association of receiving a fourth dose of the BNT162b vaccine with SARS-CoV-2 infection among health care workers in Israel. JAMA Network OPEN 2022;5:e2224657. Available at: https://pubmed.ncbi.nlm.nih.gov/35917125/. Accessed August 2022.

Fabiani M, et al. Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe COVID-19 during predominant circulation of the Delta variant in Italy: retrospective cohort study. BMJ 2022;376:e069052. Available at: https://www.bmj.com/content/376/bmj-2021-069052. Accessed March 2022.

Government of Canada. Regulatory Decision Summary – Spikevax Bivalent – Health Canada. 1 September 2022. Available at: https://covid-vaccine.canada.ca/info/regulatory-decision-summary-detail.html?linkID=RDS00987. Accessed September 2022.

Hein S, et al. Quantitative and Qualitative difference in antibody response against Omicron and ancestral SARS-CoV-2 after third and fourth vaccination. Vaccines 2022;10:796. Available at: https://pubmed.ncbi.nlm.nih.gov/35632552/. Accessed August 2022.

Link-Gelles R, et al. Effectiveness of 2, 3, and 4 COVID-19 mRNA vaccine doses among immunocompetent adults during periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 sublineages predominated – VISION Network, 10 States, December 2021-June 2022. Available at: https://pubmed.ncbi.nlm.nih.gov/35862287/. Accessed August 2022.

Magen O, et al. Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a nationwide setting. NEJM 2022;386:1603–14. Available at: https://pubmed.ncbi.nlm.nih.gov/35417631/. Accessed August 2022.

MHRA. Press release: First bivalent COVID-19 booster vaccine approved by UK medicines regulator. 15 August 2022. Available at: https://www.gov.uk/government/news/first-bivalent-covid-19-booster-vaccine-approved-by-uk-medicines-regulator. Accessed September 2022.

Munro APS, et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCOV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2 randomised trial. Lancet Infect Dis 2022;22:1131–41. Available at: https://pubmed.ncbi.nlm.nih.gov/35550261/. Accessed August 2022.

Public Health England. COVID-19 vaccine surveillance report. Week 31. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1096327/Vaccine_surveillance_report_week_31_2022.pdf . Accessed August 2022.

Pfizer. Press release: Pfizer and BioNTech granted FDA emergency use authorization of Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine booster for ages 12 years and older. 31 August 2022. Available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-granted-fda-emergency-use-authorization. Accessed September 2022.

Resource information

Respiratory conditions
  • COVID-19
Respiratory topics
  • Immunity
  • Vaccination
Type of resource
IPCRG COVID-19 and respiratory Q&A