Discussion
vaccine-type disease, PCV13-type carriage
Interest in reduced-dose schedules is growing as a more efficient way to administer PCV where vaccine-type disease has been controlled and herd protection becomes the primary aim of vaccination. Herd protection is mediated through reduction in nasopharyngeal carriage of vaccine serotypes leading to reduced pneumococcal transmission. The effect of vaccination on carriage therefore offers a good proxy measure for assessing herd protection, yet data on the effect of reduced-dose schedules on carriage are scarce. A dose in the second year of life should be sufficient to maintain herd protection,At 24 months of age, the vaccine efficacy of a 1 + 1 PCV10 schedule against PCV10-type carriage was 58% and the vaccine efficacy of a 1 + 1 PCV13 schedule against PCV13-type carriage was 65%. Similar efficacies were observed at 18 months of age (63% for 1 + 1 PCV10 and 66% for 1 + 1 PCV13). These results represent similar or greater reductions than observed following a 2 + 1 schedule of PCV10 or PCV13 in an earlier trial from the same setting.We evaluated the immunogenicity of the different schedules by ELISA and opsonophagocytic assay to establish the probable protection during the first year of life afforded by a 2-month dose of PCV, the priming effect of an infant dose of PCV on responses to a 12-month dose, and how the responses to PCV10 and PCV13 compare. The first two relate to the added advantages that a 1 + 1 schedule offers over a 0 + 1 schedule. Low-income and middle-income countries (LMICs) tend to have higher residual vaccine-type carriage following PCV introduction than high-income countries,The head-to-head product comparison shows that immune responses to a 2-month dose, both 4 weeks after PCV (by ELISA) and at 12 months of age (by ELISA and opsonophagocytic assay), tend to be better with PCV10 than PCV13, including at 12 months for the problematic serotypes 6B and 23F. These results are consistent with previous post-dose-one head-to-head data from Viet Nam,One of the strengths of this study is the inclusion of both PCV10 and PCV13 administered in two different schedules along with an unvaccinated control group. However, this strength results in multiple comparisons between groups. To overcome the multiple comparisons we have reported precise and specific microbiological outcomes, recognising that the per-comparison-wise error rate does not increase with multiple testing so adjusting for multiplicity is not necessary.In conclusion, a 1 + 1 schedule of PCV10 or PCV13 at 2 months and 12 months substantially reduces vaccine-type pneumococcal carriage during the second year of life and elicits strong immune responses. Such a schedule is likely to generate substantial herd protection along with some individual protection during the first year of life and is suitable for mature PCV programmes or for introduction in conjunction with an extensive catch-up campaign. Potentially the most effective way to deliver a 1 + 1 schedule could be a primary dose of PCV10 with a booster dose of PCV13; this regimen warrants further investigation. Reduced-dose schedules with the recently developed 10-valent PCV Pneumosil (Serum Institute of India, Pune), which has been shown to be immunologically non-inferior to PCV10 in a 3 + 0 schedule,