Science Bite (3 minute oral presentation with PPT in live session and poster) - Students and ECRs only Lorne Infection and Immunity 2023

Safety and immunogenicity of a 2+1 DTPa infant vaccination schedule in Australian infants. (#63)

Sonia McAlister 1 2 , Anita van den Biggelaar 1 2 , Ruth Thornton 1 3 , Matthew Cooper 4 , Peter McIntyre 5 , Peter Richmond 1 2 6 , Nicholas Wood 5
  1. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Australia
  2. School of Medicine, The University of Western Australia, Perth, WA, Australia
  3. Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
  4. Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
  5. National Centre for Immunisation Research and Surveillance, Sydney, NSW, Australia
  6. Departments of Immunology and General Paediatrics, Perth Children’s Hospital, Perth, WA, Australia

A 2+1 pertussis vaccination schedule administering DTPa-IPV-HBV/Hib at 6-weeks, 12-weeks, and 12-months of age may maximise early protection and improve antibody persistence into the second year of life. This may be equivalent to the current 3+1 schedule where DTPa-IPV-HBV/Hib is administered at 2, 4, 6 and 18 months. Both schedules include DTPa-IPV boosting at 4-years. We aimed to evaluate the 2+1 schedule in Australia.

Serum was collected pre- and 1-month post-primary and booster vaccinations; and during the second year of life from 82 infants. IgG- geometric mean concentrations (GMC) to pertussis-toxin (PT), pertactin (PRN), filamentous-hemagglutinin (FHA), tetanus-toxin (TT) and diphtheria-toxoid (DT) were measured using a DTPa-multiplexed bead-based immunoassay.  

The 2+1 schedule was well tolerated and immunogenic with increasing DTPa-IgG-GMC observed after each subsequent dose, except for TT for which levels remained unchanged between the first two doses.

Post-hoc analyses showed that high baseline antibody titres in infants pre-vaccination (i.e. maternally-derived) influenced immunogenicity of subsequent infant vaccines. GEE modelling of infant PT antibody responses across the first 4 years of life based on serostatus at baseline showed an average reduction in PT-IgG by 40% (p=6.6e-05). However, all children responded well to the 4-year booster, achieving antibody levels associated with seropositivity/sero-protection for all DTPa antigens.

Comparing the 2+1 schedule to a historical control cohort vaccinated with a 3+1 schedule showed that after three doses, DTPa-IgG concentrations were higher in the 2+1 group, except for FHA-IgG. During the second year of life, PT, PRN and FHA-IgG antibodies remained higher in 2+1 compared to 3+1 vaccinated infants. By 4-years of age, similar DTPa-IgG concentrations were observed between groups for all antigens. Responses to a 4-year booster were comparable between schedules, except DT-IgG was higher in the 2+1 group. All children were seroprotected throughout the study (TT- and DT-IgG≥0.01IU/mL).

These results suggest a 2+1 DTPa-schedule provides immunity into the second year of life and may induce comparable protection to the current 3+1 schedule. Given the impact of maternal antibody on infant responses, future studies should determine the optimal 2+1 schedule based on current recommendations for repeated maternal pertussis immunisation.