Real-world effectiveness of maternal genetically inactivated acellular pertussis vaccination in protecting infants under three months of age: a case-control study using concurrent community-based and test-negative controls

Abstract Purpose Infants too young for primary vaccination face the highest risk of severe pertussis and death. While maternal vaccination is the primary protective strategy, the real-world vaccine effectiveness (VE) of acellular pertussis (aP) vaccines in Thailand (including recombinant aP (aP gen )) remains unknown. We aimed to evaluate the VE of the aP vaccine in protecting infants under 3 months of age against symptomatic pertussis. Methods This case-control study was conducted in the Narathiwat Province, Thailand, during a pertussis outbreak between September 2023 and October 2024. Participants included 33 symptomatic, polymerase chain reaction (PCR)-confirmed cases, 330 asymptomatic, community-matched controls (for primary comparison), and 41 symptomatic, test-negative controls (for sensitivity simulation). Maternal vaccination with aP vaccine during pregnancy was evaluated against no pertussis vaccination. The main outcome measures were symptomatic PCR-confirmed pertussis. VEs were estimated using a logistic regression model with inverse probability of treatment weighting. Results All vaccinated mothers (98 of 404) received aP gen (94% for standalone aP gen ). The VE of the maternal aP gen vaccination against symptomatic-PCR confirmed pertussis was 95.3% (95% CI: 64.7%, 99.4%; p = 0.003). A post-hoc E-value sensitivity analysis indicated that it was unlikely that any residual or unmeasured confounders could explain away the statistically significant VE suggesting a robustness of the observed VE. Conclusion Maternal aP gen vaccination during pregnancy was highly likely to provide robust VE against symptomatic-PCR confirmed pertussis in infants during the first three months of life. These findings support the maternal pertussis vaccination with recombinant aP vaccines as effective strategy in Thailand and could be considered for other regions.