Pertussis, caused by Bordetella pertussis, is a highly contagious respiratory disease that poses a significant risk to young infants, resulting in both severe morbidity and mortality [1]. Among infants with pertussis, approximately 4% of cases are fatal. Dramatic decreases in pediatric pertussis cases and deaths have resulted from infant vaccination programs, which include whole-cell vaccines based on killed B. pertussis and acellular pertussis (aP) vaccines using highly purified B. pertussis antigens [1]. In countries with well-established childhood pertussis immunization programs, severe disease, and death predominantly occur in the first months of life in infants who are too young for vaccination.

Vaccination of pregnant women is an effective strategy to reduce disease burden in infants too young for immunization [2]. Active transfer of maternal IgG across the placenta after immunization during pregnancy provides protection to the infant during the early weeks to the first months of life [3,4]. Many countries have adopted policies for pertussis immunization in pregnancy in the second or third trimester of pregnancy [[5], [6], [7]]. Observational and randomized-controlled trials (RCTs) report significantly elevated blood antibody levels in both the mother and infant following pertussis vaccination during pregnancy, with no evidence of adverse pregnancy complications (e.g., preterm deliveries, stillbirth). In addition, the incidence of neonatal pertussis has declined in line with high maternal vaccination coverage [8,9]. A growing body of data confirms pertussis vaccination during pregnancy is highly effective in preventing infant pertussis, hospitalization, and death and has an overall positive benefit-risk ratio [10].

Combined tetanus toxoid, reduced diphtheria toxoid, and aP (Tdap) vaccines have been used for pertussis boosting in adolescents, adults, and pregnant women [1]. In these vaccines pertussis toxin (PT) is chemically inactivated (PTchem), which destroys conformational epitopes involved in toxin neutralization. This leads to an impaired functional antibody response [11], which is believed to contribute to the observed pertussis resurgence in some countries using aP vaccines [12,13]. The use of a genetically detoxified aP (aPgen) vaccine, which preserves the functionally active epitopes of PT, is proposed for the replacement of the chemically inactivated aP (aPchem) vaccine [14]. Genetic inactivation is obtained by changing two key amino acids in the S1 subunit of PT [15].

A recombinant pertussis vaccine containing genetically detoxified pertussis PT (PTgen) and filamentous hemagglutinin (FHA) is licensed as a pertussis standalone vaccine (PertagenⓇ, aPgen) and in combination with tetanus, reduced-dose diphtheria toxoids (PertagenⓇ-Td, TdaPgen) in Thailand and Singapore. In a pivotal phase 2/3 adolescent study, both aPgen and TdaPgen showed comparable safety and superior immunogenicity to Tdapchem and induced anti-PT antibodies that persisted at higher levels up to at least three years postvaccination [16,17]. In a subsequent phase 2 RCT, the immunogenicity of different doses of recombinant pertussis vaccine including licensed TdaPgen was studied in healthy nonpregnant and pregnant women and demonstrated to be safe and more immunogenic than Tdapchem [18,19]. Follow-up of infants born to pregnant women vaccinated with TdaPgen in this RCT demonstrated that compared to Tdapchem PT-IgG and PT-neutralizing antibodies were higher in infants at birth and continued to be higher at two months of age [20]. Licensed aPgen was not studied in this RCT. Postmarketing safety surveillance of aPgen and TdaPgen in Thailand, where both formulations are available for booster immunization of adolescents and adults including pregnant women, has confirmed the safety of both recombinant pertussis vaccines when given in the second or third trimester of pregnancy [21]. The use of these recombinant pertussis vaccines by pregnant women in Thailand offers the opportunity to study real-world data on infant antibody levels at birth, reflecting the placental transfer of pertussis antibodies from mothers to infants after receiving recombinant aPgen or TdaPgen in pregnancy. We conducted an observational study in which we recruited pregnant women who had opted to receive a dose of aPgen or TdaPgen vaccine during pregnancy, and measured PT neutralizing, PT-IgG, and FHA-IgG antibody levels in cord sera obtained postdelivery. This is the first study to report on the level of passive immunity against pertussis induced in infants following vaccination in pregnancy with recombinant aPgen or TdaPgen in a real-world setting and the first study overall to report such data for aPgen.

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