Research in context
infection, human infection
MAY, INFECTION, HEPATITIS A, STREPTOCOCCUS PNEUMONIA, COLD

We did an individual participant data meta-analysis (published May 4, 2023) to assess the safety of a pneumococcal controlled human infection model, searching for papers published between Jan 1, 2011, and June 30, 2022, with no language restrictions. By updating the search to April 1, 2023, we did not identify additional studies. We searched PubMed with the search terms “pneumococc*” OR “Streptococcus pneumoniae” AND “human infection model” OR “human infection stud*” OR “experimental human infection” OR “controlled human infection”. We found only one study designed to evaluate the effect of 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on experimental pneumococcal colonisation. This double-blind, randomised controlled trial, done in Liverpool, UK, established that the risk ratio of experimental pneumococcal colonisation following PCV13 vaccination compared with control vaccine (hepatitis A) was 0·22 (95% CI 0·09–0·52; p<0·001). 
We found that PCV13 was protective against experimentally induced pneumococcal carriage (serotype 6B) in healthy Malawian participants but to a lesser extent than observed in participants recruited to a similar UK-based trial. Episodes of natural pneumococcal carriage were high (42%) in our trial compared with published UK studies. We observed a greater PCV13 protective effect in participants without natural carriage (69·1%) compared with participants with natural carriage (51·7%) at the point of experimental pneumococcal inoculation. This is, we believe, the first vaccine trial that makes use of a bacterial human infection study in Africa. Our study provides important experimental data to inform epidemiological observations of high residual carriage of vaccine-serotype 
PCV13 vaccination was protective against experimental colonisation with pneumococcal serotype 6B in healthy adult volunteers from Malawi. An effective pneumococcal vaccine should interrupt population transmission through prevention of natural colonisation in vaccinated individuals. We have observed differences in protection compared with UK participants; this finding requires further evaluation by means of longitudinal immunological samples obtained from participants. Future research should pool data from the UK and Malawi populations to investigate correlates of protection. Our studies using pneumococcal controlled human infection could suggest means to improve schedules for current vaccines and to test prospective pneumococcal vaccines relevant to populations that need them most.Vaccine efficacy is often reduced in low-resource settings compared with high-income countries. There are many reasons why this might be the case, including vaccine acceptability and uptake, and health systems issues such as cold chain integrity, high force of infection (high carriage rates in the community), pathogen diversity, and host immunity. In the case of the observed reduced herd effect following PCV13 implementation in infants in Malawi, it has been suggested that force of infection might explain the residual vaccine-type carriage in vaccinated children.We previously developed a controlled In this study, we aimed to use the EHPC CHIM to establish the vaccine efficacy of PCV13 against experimental pneumococcal carriage in young healthy adults in Malawi.