Do Influenza Vaccines That Are Mismatched to Flu Viruses Protect Children?

Influenza vaccine
Influenza vaccine
How well do influenza vaccines protect children against critical and life-threatening illness when vaccines are mismatched with the virus?

During the 2019 to 2020 influenza season, when vaccine-mismatched influenza viruses predominated, vaccination was associated with reduced risk for life-threatening and critical illness in children, according to research findings published recently in Clinical Infectious Diseases.

Researchers sought to determine how well vaccines protected against critical influenza virus in children when the vaccine was mismatched with the virus, as was the case during the 2019 to 2020 influenza season. The investigators identified participants by influenza testing and sequencing children less than 18 years of age with acute respiratory infection admitted to intensive care units of 17 hospitals. All patient respiratory specimens underwent reverse transcription polymerase chain reaction influenza testing. Vaccine effectiveness was assessed by comparing odds of vaccination in test-positive cases vs in test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation.

Critically ill children (under 18 years of age) included in the study were separated into 2 cohorts,  a case patient cohort of 159 children who tested positive for influenza (median age 6 years) and a control cohort of 132 patients who tested negative (median age 4 years). In the case patient cohort, the researchers found 51% A/H1N1pdm09 and 25% B-Victoria viruses.  Among the 56 sequenced A/H1N1pdm09 viruses, 52% were vaccine-mismatched and 41% were vaccine-matched. Among sequenced B-lineage viruses, the majority (30 of 31) were vaccine-mismatched.

The analysis found that vaccine effectiveness was 63% against critical illness from any influenza virus; 64% against critical illness from A(H1N1)pdm09; and 68% against B-lineage viruses. Notably, protection did not differ by age group or by full vs partial vaccination. Researchers also found vaccine effectiveness was 75% against life-threatening influenza and 57% against non-life-threating influenza. Effectiveness was 78% against matched A(H1N1)pdm09 viruses, 47% against mismatched A(H1N1)pdm09 viruses, and 75% against mismatched B-Victoria viruses.

Researchers noted, “In this study of critically ill children with [acute respiratory infection], we estimate that vaccination effectively reduced life-threatening influenza illness by 75% during a season predominated by B/ Victoria viruses and A/H1N1pdm09 subclade viruses that were antigenically drifted from vaccine components.” They added that “Our real-world findings suggest that accelerating efforts to bring influenza vaccines to all children could lead to appreciable reductions in critical illness and deaths from influenza worldwide.”

Disclosure: This research was supported by the CDC under a contract to Boston Children’s Hospital. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Olson SM, Newhams MM, Halasa NB, et al. Vaccine effectiveness against life-threatening influenza illness in US children. Clin Infect Dis. Published online January 13, 2022. doi:10.1093/cid/ciab931

This article originally appeared on Pulmonology Advisor