Boostagen-2 Mechanism of Action

Pharmacology: Immune response: Non-inferiority of the immune response of Boostagen-2 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 Boostagen-2 Tdap_gen than with Tdap_chem vaccine. Hence, non-inferiority of Boostagen-2 was met as recommended in WHO TRS 979. In addition, superiority of Boostagen-2 was also demonstrated for pertussis seroresponse rates and GMTs in accordance with EMA guidelines (CPMP/EWP/482/99). (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 rapid waning of immunity and a short duration of protection conferred by Tdap_chem (US CDC, 2018). An alternative means suggested to reduce waning is to use pertussis toxin (PT) which has been genetically detoxified (PT_gen) rather than chemically detoxified (PT_chem) in vaccines (IMAC, 2018).
The antibody persistence one year after one dose of Boostagen-2 was evaluated against a Tdap_chem comparator. Boostagen-2 induced a higher anti-PT booster response persisting in 60% of adolescents as opposed to 20% with Tdap_chem vaccine (Table 2). (See Table 2.)

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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). Data on the effectiveness of Boostagen-2 against pertussis are not yet available.
In a pivotal study, adolescents who received Boostagen-2 Tdap_gen induced significantly higher anti-PT antibodies than the ones who received a Tdap_chem comparator of which effectiveness was evaluated (Tables 1 and 2). The 2.6-fold higher anti-PT titers persist after 1 year, which may confer higher immunity and longer duration of protection in adolescents (Table 3). (See Table 3.)

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Maternal vaccination during pregnancy confers protection to infant. Transplacental transfer of maternal pertussis antibodies from mother to infant provides some protection against pertussis in early life (US CDC, 2017).
In a randomized controlled trial, Boostagen-2 induced a 4-fold increase in maternal anti-PT neutralizing antibodies in 83% pregnant women vaccinated in the second or third trimester of pregnancy as opposed to 71% with a Tdap_chem comparator. These maternal antibodies were transferred to neonates with a GMT ratio when compared to Tdap_chem above 1 in neonates at birth (Table 4). (See Table 4.)

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