Discussion
human infection
We have shown in a double-blind, randomised controlled trial, which made use of a human infection study that PCV13 has a protective effect against experimental pneumococcal carriage in healthy young Malawian adults. This is an important result because of the disappointingly high rates of vaccine-type pneumococcal carriage in our context, following national vaccine roll-out. The study offers both reassurance in showing a vaccine effect, and an explanation for the observed persistent carriage in showing a reduced vaccine effect associated with natural carriage at the time of experimental inoculation. It could be that high rates of natural carriage lead to reduced vaccine effectiveness. This is also a landmark study in that it is, to our knowledge, the first vaccine trial that makes use of a bacterial human infection study in Africa.There are similarities and differences between our study and the experimental human carriage randomised controlled trial of PCV13 published in Liverpool.The first major difference in the human infection studies in Malawi and Liverpool was that more Malawian participants were male compared with the Liverpool study (72% male in Malawi The second major difference between the UK and Malawi was the difference in natural carriage. In Malawi, more participants had natural pneumococcal carriage during the study than in Liverpool. 42% of young Malawian adults had an episode of natural carriage during the 2 months of the study compared with only 6% in LiverpoolIn the context of the experimental model, these observations suggest that the ecological niche into which the experimental inoculum is pipetted is a determinant of success or otherwise in establishing experimental carriage. There are other data to support this hypothesis. We have described nasopharyngeal microbiomes in which high diversity was associated with experimental carriage, and lower diversity with less carriage.A limitation of our study is the low rate of experimental carriage that was achieved. We increased the inoculation dose to twice that used in Liverpool. Further, we modelled the dose–response function (The primary purpose of this study was to establish, by means of a human infection study, whether PCV13 was protective against carriage in Malawian adults. This result was clear and showed that vaccination does protect against carriage. This result has been shown to be similar in both Liverpool, UK and Blantyre, Malawi, suggesting that the result is generalisable, albeit with consideration of sex and natural carriage incidence. PCV13 boosts circulating anticapsular IgG,

