Search

• Recombinant pertussis vaccine is safe for both mother and newborn. • There is effective transplacental antibody transfer to infants at birth. • No difference in antibody response is shown during 2nd or 3rd trimester of pregnancy. Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PT gen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PT gen and 1 µg FHA (ap1 gen), or Td combined with ap1 gen (Tdap1 gen), or with 2 µg PT gen and 5 µg FHA (Tdap2 gen), or with 5 µg PT gen and 5 µg FHA (TdaP5 gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8 chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. Anti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5 gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8 chem (98.75% CI) was significantly higher for TdaP5 gen (2.6 [1.7–4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. BioNet licensed (TdaP5 gen and Tdap2 gen) and candidate vaccines (Tdap1 gen and ap1 gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants. [ABSTRACT FROM AUTHOR]

• Recombinant inactivated pertussis vaccines are safe in non-pregnant women. • Lower-dose genetically-inactivated pertussis toxin has comparable immunogenicity. • Monovalent recombinant pertussis vaccine shows favorable immunogenicity and safety. A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PT gen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PT gen and 1 μg FHA (ap1 gen), tetanus, reduced-dose diphtheria (Td) combined to ap1 gen (Tdap1 gen) or combined to recombinant pertussis containing 2 μg PT gen and 5 μg FHA (Tdap2 gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PT gen and 5 μg FHA (Boostagen®, TdaP5 gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PT chem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8 chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1 gen , 88% (95% CI 76–95) for Tdap1 gen , 80% (95% CI 66–90) for Tdap2 gen , 94% (95% CI 83–99) for TdaP5 gen , and 78% (95% CI 64–88) for Tdap8 chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004. [ABSTRACT FROM AUTHOR]