Three-Dose Hybrid Immunity Provided Older Adolescents With Robust Protection Against SARS-CoV-2 Infection


Infection-induced immunity with 2-dose vaccination still offered protection against the circulating variant.

Hybrid immunity gained from previous SARS-CoV-2 infection and 3 COVID-19 mRNA vaccine doses offered more protection for adolescents against the circulating omicron (BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than infection alone, according to authors of a recent study published in Pediatrics.

In conjunction, protection from infection-induced immunity and vaccination helped to reduceCOVID-19 surges in the student population. Without either infection-induced or vaccine-induced immunity, “the school-level impact of the BA.1 surge on students may have been much worse,” wrote the study authors.

There is limited data on vaccine efficacy for children and adolescents and the vaccine’s influence on infection rates in the school setting, so investigators aimed to determine the efficacy of the COVID-19 mRNA vaccine in children and adolescents, with or without previous infection. When data was collected (January 2022), the primary SARS-CoV-2 variant in circulation was omicron (BA.1).

The cohort included 17,910 students in middle and high school students aged 12 to 19 years. Among the cohort, 16.7% of students had previously documented COVID-19 infection; 55.6% received 2 vaccine doses within 211 days of the study, and 8.6% of students aged 16 to 19 years received 3 vaccine doses.

Previous infection and 3 vaccine doses (3-dose hybrid immunity) was linked to the highest level of protection, according to the study authors. The 3-dose hybrid immunity offer 70.0% protection to students aged 16 to 19 years (95% CI: 42.3%–84.5%), although confidence intervals overlapped with previous infection or vaccination alone. For students aged 16 to 19 years who had no previous infection, 3 vaccine doses provided 44.2% protection.

“The addition of a third dose increased protection regardless of previous infection status, highlighting the importance of booster doses,” study authors wrote.

Protection from 2-dose hybrid immunity (if the dose was administered less than 180 days) was higher in younger adolescents aged 12 to 15 years (58.7% [95% CI: 33.2%–74.4%] compared to students aged 16 to 19 years (54.7% [95% CI: 31.0%–70.3%]). The 2-dose hybrid immunity only offered noticeable protection benefits within 180 days of receiving the second dose.

Previous infection alone was still associated with protective benefits; it offered 35.9% (95% confidence interval [CI]: 12.9%–52.8%) protection in adolescents aged 12 to 15 years and 23.8% (95% CI: 2.1%–40.7%) protection to students aged and 16 to 19 years.

The authors noted that there are limitations to this study. First, not enough students aged 12 to 15years received 3 vaccine doses, which prevented 3-dose hybrid immunity analysis. In addition, vaccine effectiveness might have been underestimated, as there was a risk of false-negatives. Additionally, the data do not include all state- or individual-level characteristics and the generalizability of the findings may be limited.

In the study, the authors list prevention strategies that can curb disease spread, such as regular screening testing, physical distancing, and masking. They additionally noted that more studies should evaluate the efficacy of booster vaccines for children and adolescents and the role of vaccination in ameliorating other burdens associated with the disease.

“Real-world [vaccine effectiveness] estimates can guide the prioritization of resources and help focus messaging needed, particularly at the state and local levels to protect against the risk of infection,” study authors wrote.


Almendares OM, Ruffin JD, Collingwood AH, et al. Previous Infection and Effectiveness of COVID-19 Vaccination in Middle- and High-School Students. Pediatrics. December 2023;152 (6): e2023062422. 10.1542/peds.2023-062422

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