Effect of reduced two-dose (1+1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (SynflorixTM and Prevenar13TM)) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life: Results from an open-labelled randomized controlled trial in Indian children.

Abstract

This study aimed to assess the effect of a reduced dose regime (1+1) of PCV10 and PCV13 along with 3-dose regimes on pneumococcal vaccine-type (VT) carriage and immunogenicity in the first two years of life in PCV-naïve Indian children. A total of 805 healthy infants aged 6-8weeks were randomised to 7 groups (n=115). Six groups received SynflorixTM(PCV10) or Prevenar13TM(PCV13) in the following schedules: 3+0 (three primary at 6, 10, and 14weeks); 2+1 (two primary 6 and 14weeks with booster at 9months; 1+1 (one primary at 14weeks with booster at 9months). The 7th group was a PCV-naïve control group. Nasopharyngeal swabs were collected at 6, 18weeks, 9, 10, 15, and 18months of age. Venous blood samples were collected at 18weeks, 9, 10, and 18months of age for assessment of sero-specific IgG antibodies. Additionally, functional activity using a serotype specific opsonophagocytic assay (OPA) was assessed at 10 and 18months of age in a subset (20%) of participants. All schedules of PCV13 showed significant 13VT carriage reduction in the second year of life as compared to control. At 15months of age, PCV13 (1+1) showed 45% reduction in 13VT-carriage compared to the control [OR=0.55 (95% CI; 0.31-0.97), p=0.038]. None of the PCV10 schedules showed significant reduction in 10VT carriage in the second year. Although not powered for these outcomes, at 18months of age, 1+1 and 2+1 schedules of both vaccines demonstrated higher sero-responders for all serotypes, higher geometric mean concentrations (GMC) for all serotypes except 23F [with both vaccines], higher percent OPA responders and OPA geometric mean titres (GMT) compared to the 3+0 schedules for all serotypes. The reduced dose schedule (1+1) of PCV13 results in significant VT-carriage reduction in the second year of life. Immune protection provided by 1+1 schedules of PCV10 and PCV13 in the second year of life is comparable to WHO-recommended 3-dose schedules.