Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) 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.
Methods
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 PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, 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.
Results
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 TdaP5gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (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.
Conclusions
BioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.
1. Introduction
Pertussis vaccination during pregnancy for prevention of early infant mortality is recommended by the World Health Organization in case of resurgence of pertussis or in countries with high or increasing infant morbidity/mortality from pertussis [1].
Pertussis immunization in pregnancy leads to active transport of maternal immunoglobulin G (IgG) antibodies across the placenta beginning in the second trimester to protect the infant during the first months of life [2].
Pertussis vaccination during pregnancy is supported by observational and randomized-controlled studies reporting significantly elevated blood antibody levels in both the mother and newborns at birth compared with those who received placebo or no vaccination, with no indication of increased risk of adverse pregnancy complications [3], and evidence that severe disease in infants may be prevented [4], [5]. Many high-income countries and countries in Latin America have adopted policies for maternal pertussis immunization (MPI), in the second or third trimester [1], [6], [7], [8] whereas, in low- and middle-income countries (LMIC), MPI is not implemented because of unclear disease burden [9], vaccine pricing, and supply constraints.
Although an immunologic correlate of protection has not been established for pertussis vaccines, the demonstrated efficacy in the context of both primary and booster immunization of vaccines containing only inactivated pertussis toxin (PT), which is a key virulence factor for Bordetella pertussis, indicate that immune responses to this antigen are essential [10].
Indeed, all acellular pertussis (aP) vaccines (APV) contain a PT component and nearly all of them include filamentous haemaglutinin (FHA) as well [11]. Two-component APV (PT and FHA) have been widely used in infants and have been combined with diphtheria and tetanus toxoids (DT or Td). APV differ not only in the number and concentration of the antigen components but also with regard to the bacterial clone used in production and methods of purification and detoxification (chemical or genetic) [1].
Given the potentially detrimental effects of chemical detoxification on epitope preservation [12], genetically inactivated PT (PTgen) containing vaccines using recombinant DNA technology have been compared to chemically inactivated acellular pertussis vaccines [13]. Earlier studies demonstrated that the genetically inactivated pertussis vaccines had higher immunogenicity than the chemically inactivated pertussis vaccines while having similar reactogenicity [11], [14].
aP5gen is a two-component recombinant acellular pertussis vaccine containing 5 µg of recombinant pertussis toxin (rPT or PTgen) and 5 µg of FHA, developed and manufactured by BioNet (Thailand) and licensed as monovalent (Pertagen, aP5gen) or combined vaccines (Td-Pertagen/Boostagen®, TdaP5gen) in Thailand [15] and Singapore. Safety and non-inferior and superior immunogenicity of both vaccines to a licensed comparator were shown in a phase 2/3 randomized controlled trial in adolescents [16]. The long-lasting immunity induced by the two vaccines were also confirmed in a three-year pertussis antibody persistence study [17].
Due to its higher immunogenicity, it is possible that vaccines containing a lower dose of PTgen could provide comparable immunity to chemically inactivated pertussis vaccines for maternal vaccination, reducing cost and making vaccine more accessible in developing countries.
Two randomized controlled trials, one in women of childbearing age and one in pregnant women, comparing monovalent (pertussis-only ap) or combined vaccines (Tdap/TdaP) with different concentrations of PTgen showed the vaccines were safe and non-inferior to Tdap8chem (Boostrix™; GlaxoSmithKline Biologicals, Belgium) [18], [19]. The present report describes the follow up of pregnant women at the time of delivery and their newborns at birth and before any pediatric pertussis vaccination, determining pregnancy outcomes and transferred immunity to infants.
Source: ScienceDirect
