Mucosal immune responses to Bordetella pertussis in Gambian infants after maternal and primary vaccination: an immunological substudy of a single-centre, randomised, controlled, double-blind, phase 4 trial

BACKGROUND: 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. METHODS: 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. FINDINGS: 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