Pertussis, also known as whooping cough, is an acute respiratory disease caused by Bordetella pertussis, a bacterium that is transmitted between people primarily through aerosolised respiratory droplets generated by coughing or sneezing.1 Common symptoms include cough for a mean duration of 10 weeks, paroxysms, post-tussive apnoea, and post-tussive vomiting.2 Sinusitis, pneumonia, and neurological complications affect 0·05–0·3% of cases.2, 3 Pertussis causes substantial morbidity in adolescents and can have social and economic consequences by disrupting school and work attendance.4 Adolescents can also be a source of infection for infants and young children and other high-risk populations.3
Acellular pertussis vaccines all contain pertussis toxin (PT) antigen, and anti-PT neutralising antibodies are crucial to prevent pertussis disease; in addition, acellular pertussis vaccines can contain a combination of filamentous haemagglutinin (FHA), pertactin, fimbriae type 2, and fimbriae type 3.5, 6, 7, 8 Unlike chemical inactivation of PT, which alters the conformational epitopes and affects vaccine-induced antibody responses,9 recombinant PT that has been genetically inactivated conserves the native antigen structure.10 A new-generation monovalent recombinant acellular pertussis vaccine containing 5 μg PT and 5 μg FHA (aPgen) is licensed for immunisation of individuals aged 11 years and older. aPgen combined with tetanus and reduced-dose diphtheria toxoids (TdaPgen) has been licensed for immunisation of individuals aged 3 years and older in Thailand since 2016.11 In clinical trials, both aPgen and TdaPgen were more immunogenic 28 days after vaccination than the chemically inactivated version of the combined vaccine (Tdapchem),6, 12 and antibody responses to booster doses of aPgen and TdaPgen remained relatively high for 2–3 years after booster vaccination.13 Vaccination with aPgen was also associated with increased PT-specific memory B-cell responses.12
Protection by pertussis vaccines wanes over time.14 Consequently, booster vaccination is recommended in adolescents, adults, and pregnant women.15 In the USA, the rising incidence of pertussis among adolescents in 2004 prompted the Advisory Committee on Immunisation Practices (ACIP), in 2005, to recommend that adolescents receive a single booster dose of Tdap vaccine after completion of the childhood vaccination series with whole-cell or acellular pertussis-containing vaccine.16 In 2018, the recommendations were updated to include adults who had not received Tdap and pregnant women.15 In 2019, ACIP also recommended either the combined tetanus- diphtheria (Td) vaccine or Tdap for the decennial Td booster and tetanus prophylaxis for wound management.17 In 2015, WHO suggested booster vaccination in adolescents be implemented after consideration of local epidemiology and cost effectiveness.18 The acellular pertussis vaccine is associated with fewer adverse events than the whole-cell pertussis-containing vaccine, so the past two decades have seen an increasing trend to adopt acellular pertussis vaccines for children and introduce boosters for adolescents.19 However, a growing body of evidence suggests that the change from whole-cell pertussis-containing vaccines to chemically inactivated pertussis vaccine (apchem) is responsible for the rapid waning of pertussis immunity and progressive decline of PT boostability.18 In a meta-analysis, apchem vaccine effectiveness in adolescents aged 11–19 years at the time of vaccination was 72% at 1 year after booster vaccination and 42% at 4 years.14
A recombinant pertussis booster vaccine that induces durable pertussis immunity without additional side-effects could improve acceptance. Reduced-dose versions of the vaccines, namely vaccines containing recombinant reduced-dose PT (2 μg) and FHA (5 μg) combined with tetanus toxoid, reduced-dose diphtheria toxoid (Tdapgen) and monovalent pertussis vaccine containing recombinant reduced-dose PT (2 μg) and FHA (5 μg) alone (apgen).could, in turn, lower vaccine costs, which could benefit people in low-income and middle-income countries where vaccine cost is a crucial consideration in determining which vaccines to include in national immunisation programmes.20 The aim of this study was to evaluate the safety and immunogenicity of reduced-dose apgen and Tdapgen vaccines containing 2 μg recombinant PT.
Source: Science Direct
