Boostagen Mechanism of Action

Pharmacotherapeutic group: Purified antigen, combinations with toxoids. ATC code: J07AJ52.
Pharmacology: Pharmacodynamics: Immune response: Immunogenicity of Boostagen (TdaP_gen) was evaluated in six randomized controlled trials including 413 persons ranging in age 3 to 75 years old (20 children, 149 adolescents, 244 adults including 119 pregnant women and 15 older adults).
In all conducted randomized controlled trials, Boostagen was found to be more immunogenic than Tdap_chem comparator vaccines with significantly higher PT-IgG titers one month after vaccination. The summary of five of these trials is provided in Table 1.
Non-inferiority of the immune response of Boostagen was demonstrated in adolescents one month after vaccination in a comparative randomized controlled trial (Table 1). Seroprotection rates of tetanus and diphtheria toxoids were similar to the Tdap_chem comparator. The pertussis antibody booster response and titers were significantly higher after vaccination with TdaP_gen than with Tdap_chem vaccine. Hence, non-inferiority of Boostagen was met as recommended in WHO TRS 979. In addition, superiority of Boostagen was also demonstrated for pertussis seroresponse rates and GMTs in accordance with EMA guidelines (CPMP/EWP/482/99). One trial in children found that Boostagen was immunogenic when compared to pediatric DTaP_chem containing vaccine. (See Table 1.)

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Antibody persistence: There are no well-established antibody levels which correlate absolutely with pertussis protection. However, the rapid decline in antibody levels during the first year observed with Tdap_chem vaccines is consistent with the epidemiologic and vaccine effectiveness data in adolescents that indicated its rapid waning of immunity and a short duration of protection (US CDC, 2018). An alternative means suggested to reduce waning is to use pertussis toxin which has been genetically detoxified rather than chemically detoxified in vaccines (IMAC, 2018).
The antibody persistence after one dose of TdaP_gen was evaluated against a Tdap_chem comparator (Table 2). One year after booster vaccination with Boostagen, 98% of adolescents had anti-PT IgG titers compared to 50% in Tdap_chem comparator. Boostagen also induced a higher neutralizing antibody response persisting in 85% of adolescents at year 3 as opposed to 43% with Tdap_chem vaccine.
Long-term antibody persistence was shown in adolescents five years after vaccination with Boostagen with 56% of vaccinees retaining high PT-IgG levels (≥20 IU/mL), as opposed to 27% of vaccinees that received a licensed vaccine. (See Table 2.)

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Passive protection against pertussis in infants born to mother vaccinated during pregnancy: Boostagen were evaluated in pregnant women in three studies (Table 1 and 3) and compared to two different Tdap_chem comparator vaccines and a control Td vaccine: Boostagen induced significantly higher PT neutralizing antibody (PTNA) titers and PT-IgG and FHA-IgG antibody concentrations than a comparator Tdap_chem vaccine in pregnant women one-month post vaccination.
Boostagen induced PT-IgG antibody concentrations non-inferior to a comparator Tdap_chem vaccine in pregnant and non-pregnant women.
Boostagen induced maternal pertussis antibodies that were effectively transferred at high levels to infants and remained high in infants until at least 2 months after birth (Table 3).
There were no significant differences in pertussis antibody responses between Boostagen between non-pregnant and pregnant women, or between vaccination in the second or third trimester of gestation. (See Table 3.)

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Maternal pertussis immunization may interfere with infants' immune response to primary pertussis immunization. However, no evidence suggests a clinical impact of such immunological interference on protection against pertussis.
Immune response in immunocompromised population: Maternal immunization with Boostagen resulted in comparable high PT-IgG antibody concentrations in infants born to HIV-infected or non-infected pregnant women.
Protection against Pertussis: Immunological correlates of protection against pertussis are not well-defined, but higher levels of anti-pertussis antibodies are associated with greater protection. Present knowledge indicates that PT, particularly if genetically detoxified, represents the main antigen that protects against severe pertussis disease.
Boostagen induces significantly higher anti-PT antibody titers than licensed Tdap_chem vaccines for which effectiveness is documented.
Boostagen induced anti-PT antibody titers are significantly higher and persist at significantly higher levels for at least five years, conferring higher and longer duration of protection than licensed comparator Tdap_chem vaccine.
Maternal vaccination is a highly effective strategy to protect infants against pertussis infection through both transfer of maternal pertussis antibodies and reduced infant exposure to pertussis. Vaccination of pregnant women with Boostagen induces high titers of PT-neutralizing antibodies that are effectively transferred to their infants.
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
Toxicology: Preclinical safety data: General toxicity: Preclinical data of Boostagen reveal no special hazard for humans based on conventional studies of single-dose toxicity and repeat-dose toxicity in rats.
Genotoxicity/Carcinogenicity: Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine are not expected to have genotoxic potential.
Reproductive and Developmental toxicity: Two prenatal and postnatal developmental toxicity studies of Boostagen show no toxicity effect on maternal pregnancy, parturition, lactation, embryo-foetal development and reproductive performance in rats.