Scientific reportsOct 8, 2025

How well and how long a fourth dose of original mRNA COVID-19 vaccines protects against infection in Qatar

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A fourth ancestral-strain mRNA COVID-19 vaccine dose gave only modest, short-lived added protection against SARS-CoV-2 infection in Qatar.

Evidence

This nationwide matched cohort study compared four versus three BNT162b2 or mRNA-1273 doses from February 10, 2021 to May 13, 2024, estimating adjusted hazard ratio 0.91 and relative vaccine effectiveness 9.2%, peaking at 35.0% in the first three months.

Caveat

Protection became negligible after three months, and the study assessed infection during omicron subvariant circulation rather than durable protection from updated vaccines.

Simplified

Concerns about waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the emergence of new variants underscore the need for booster doses. Using a matched cohort design, this study evaluated the relative effectiveness and durability of a fourth dose of ancestral-strain mRNA vaccines (BNT162b2 or mRNA-1273) in preventing SARS-CoV-2 infection, compared to three doses, between February 10, 2021 and May 13, 2024 in Qatar. The fourth dose conferred modest additional protection against infection, with an adjusted hazard ratio for infection of 0.91 (95% CI: 0.81-1.02), corresponding to a relative vaccine effectiveness of 9.2% (95% CI: - 1.7 to 18.9%). Protection peaked within the first three months of vaccination at 35.0% (95% CI: 20.6-46.8%) but waned rapidly thereafter, becoming negligible beyond that period. These findings highlight the modest and short-term protection of ancestral-strain vaccines against omicron subvariants and support the need for next-generation vaccines offering more durable immunity.

Key numbers

0.91

Adjusted Hazard Ratio for Infection

Comparison of four-dose vs. three-dose

9.2%

Effectiveness of fourth dose compared to three doses

35.0%

Peak Protection Duration

Protection within the first three months post-vaccination

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Funding

Competing interests

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PubMed

How well and how long a fourth dose of original mRNA COVID-19 vaccines protects against infection in Qatar

Abstract

Key numbers

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Competing interests

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