ArticleThe Lancet regional health. Southeast Asia2025
Durability of protection of ancestral-strain COVID-19 third- and fourth-dose vaccine boosters against Omicron XBB/XBB.1 and JN.1 symptomatic infection, hospitalisation and mortality in Indonesian adults (2023-2024): a test-negative case-control study.
Article in The Lancet regional health. Southeast Asia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: SARS-CoV-2 ancestral-strain vaccines have effectively reduced SARS-CoV-2-related severe illness and death worldwide. However, waning immunity over time has warranted revaccination to boost immunity. Indonesia, like most low- and middle-income countries, has not provided regular vaccine boosters post-pandemic. This study assessed the longer-term durability of protection from ancestral-strain third- and fourth-dose boosters. Methods: We conducted a test-negative case-control study among symptomatic adults seeking SARS-CoV-2 testing at 14 purposely selected test sites in the major cities of Yogyakarta and Jakarta (March 2023-May 2024). Test-positive individuals were cases and test-negative individuals were controls. SARS-CoV-2 variants were identified using whole genome sequencing. We used multivariable logistic regression to estimate absolute or incremental vaccine effectiveness (VE) against symptomatic infection and COVID-19-related hospitalisation or death, adjusted for main confounders. Findings: Of 2439 participants (median age 35 years, 56.2% female), 388 were cases and 2051 controls. Vaccination with two primary doses, a third-dose or fourth-dose booster did not provide sustained protection against Omicron XBB/JN.1 symptomatic infection up to median 27, 20 or 13 months since administration, respectively. However, there was sustained incremental protection from the third-dose booster (administered median 20 month prior) against hospitalisation (VE 38.3% [95% CI 3.9-60.3]) and death (55.2% [17.7-75.6]) for older individuals (aged >50 years), and against death (55.2% [12.8-76.9]) for individuals with one or more comorbidities. There was also sustained incremental protection from the fourth-dose booster (administered median 13 months prior) against hospitalisation for older individuals (50.2% [10.3-72.3]) and individuals with one or more comorbidities (74.4% [49.2-87.1]). Interpretation: Ancestral-strain vaccine boosters provided durable, moderate protection against severe or fatal outcomes from Omicron XBB/JN.1 infection for older and comorbid individuals. The findings highlight the benefits of improving access to revaccination for vulnerable groups in Indonesia. Funding: US Centers for Diseases Control and Prevention.
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