Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus-diphtheria-acellular pertussis-inactivated poliovirus; Tdap-IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy. This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18-40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap-IPV) vaccine or a TT-only vaccine at 28-34 weeks' gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria-tetanus-whole-cell pertussis (DTwP) vaccine or a diphtheria-tetanus-acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-B pertussis IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with ClinicalTrials.gov, NCT03606096. This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap-IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22-4·59]; p<0·0001) and anti-B pertussis IgG (6·45 [5·94-7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-B pertussis IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79-7·75], p=0·0036 for the TT-DTwP group and 4·40 AU/mL [2·99-6·45], p=0·024 for the Tdap-IPV-DTwP group vs 2·16 AU/mL [1·40-3·32] for the Tdap-IPV-DTaP group). Furthermore, DTaP-vaccinated infants born to mothers who had received the Tdap-IPV vaccine in pregnancy had the lowest anti-B pertussis IgG concentrations, even those who had low concentrations of maternally derived antibodies pre-vaccination. Similarly, compared with TT immunisation, Tdap-IPV immunisation in pregnancy was associated with lower nasal anti-pertussis toxin IgG responses in infants after completion of both DTwP and DTaP primary immunisation series at age 20 weeks, although this blunting was more pronounced after DTwP vaccination (GMC 0·016 international units [IU] per mL [0·011-0·025] for the Tdap-IPV-DTwP group vs 0·073 IU/mL [0·044-0·120] for the TT-DTwP group [p=0·0002] and 0·021 IU/mL [0·014-0·032] for the Tdap-IPV-DTaP group vs 0·058 IU/mL [0·041-0·081] for the TT-DTaP group [p=0·0016]). Broad nasal T-cell-associated cytokine responses were observed after primary vaccination in DTwP-vaccinated but not DTaP-vaccinated infants, with no clear impact of the vaccine given in pregnancy. Tdap-IPV vaccination during pregnancy induces antibodies that are transferred across the placenta to reach the upper airway mucosa of the infant and could contribute to local protection. Although maternally derived antibodies modulate pertussis toxin-specific IgG responses to primary vaccination in the infant, those who received the DTwP vaccine consistently generated higher mucosal IgG to whole-cell B pertussis and showed stronger local cellular activation than those who received the DTaP vaccine, corroborating DTwP-specific mucosal effects identified from animal studies. Taken together, these findings provide mechanistic support for the established early-life protection conferred by immunisation during pregnancy and demonstrate the broader mucosal immunity elicited by DTwP vaccination, informing policy discussions on antenatal vaccination programmes and infant pertussis vaccination schedules. The Innovative Medicines Initiative 2 Joint Undertaking, Horizon 2020, European Federation of Pharmaceutical Industries and Associations, Gates Foundation, Wellcome Trust, and BactiVac.
使用 AI 将内容摘要翻译为中文，便于快速阅读
使用 AI 分析这篇文章的核心发现、关键要点和深度见解
由 DeepSeek AI 提供分析 · 首次使用需配置 API Key
Science Daily Tech · 2026-05-09
Science Daily Tech · 2026-05-08
Ars Technica · 2026-05-09