boostagen Mechanism of Action

Pharmacology: Immune response: 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). Boostagen TdaP_gen was also found immunogenic in children aged 3 to 7 years old in a comparative randomized controlled study with a pediatric DTaP_chem-IPV containing chemically detoxified PT and FHA. (See Table 1.)

Click on icon to see table/diagram/image

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. Boostagen also induced a higher neutralizing antibody response persisting in 85% of adolescents at year 3 as opposed to 43% with TdaP_chem vaccine. (See Table 2.)

Click on icon to see table/diagram/image

Protection against Pertussis: Although there is no current correlate of protection to pertussis antigens, induction of anti-PT antibody was shown to induce protection (WHO, 2017). When compared to three different chemically-detoxified pertussis vaccines (2, 3 and 5-component pertussis vaccines in 5 randomized clinical trials, Boostagen induced significantly higher anti-PT antibody response in children, adolescents and adults (Tables 1 to 4). This response was similar in non-pregnant and pregnant women when Boostagen was given in the 2^nd and 3^rd trimester of gestation. (See Table 3.)

Click on icon to see table/diagram/image

In one observational study evaluating the pertussis maternal immunization, anti-PT antibodies in cord sera were higher in 200 mothers immunized with Boostagen TdaP_gen than in the mothers who received Td vaccine with the respective titers, 153 IU/mL (129-181) vs 6 IU/mL (4.8-8.7) demonstrating the maternal anti-PT antibodies transfer to the newborn.
In adolescents, Boostagen induces 3 to 7-fold higher anti-PT titers that persist after 3 years, which may confer higher immunity and longer duration of protection in adolescents (see Table 4).

Click on icon to see table/diagram/image