35 mcg/mL of type specific antibody), understood not as an individual level surrogate but instead as a measure in a group of vaccinated children that would be “predictive of protection”, was accepted by numerous licensing bodies, but was not derived on a serotype specific basis. In 2003 the Bill & Melinda Gates Foundation, with various Afatinib partners, issued the Grand Challenges in Global Health (GCGH) initiative. Led by the late Helena Mäkelä and by Hanna Nohynek, the PneumoCarr Consortium was formed and funded by the

GCGH initiative to address the roadblocks to the licensure of novel pneumococcal vaccines. The PneumoCarr Consortium, made up of researchers from around the world with expertise in the field of pneumococcal colonization following PCV, Libraries proposed as a solution to this roadblock the use of pneumococcal colonization impact as an alternative biological licensure endpoint instead of IPD. The advantage gained would be enormous in terms of both sample size required and ease of endpoint detection. This approach has furthermore the beauty of measuring the impact on the pathogen (as opposed to immunogenicity), focusing on the first and necessary step of pneumococcal infection (i.e. colonization

with pneumococcus) and measuring the total community public health impact of pneumococcal vaccine (i.e. incorporating the transmission of the bacteria measured as colonization or acquisition of carriage in the unvaccinated community members). Our goal thus was to establish whether measuring prevention of

pneumococcal colonization could serve Kinase Inhibitor Library as a central component of pneumococcal vaccine licensure approaches and clinical vaccine effectiveness measures. During the project work (2006–2012) the research on and implementation of pneumococcal vaccines made huge advances, and accordingly the PneumoCarr project updated it’s aims and goals, but the original idea of using colonization as an endpoint in pneumococcal vaccine evaluation remained unchanged. It was highlighted that colonization could be used to evaluate both the direct and especially indirect vaccine effects with the latter emphasized because of the quantitative public health benefit of reductions in vaccine serotype pneumococcal disease throughout the population and because of unintended increases in non-vaccine no serotype disease (i.e. replacement disease). The focus on pneumococcal colonization suggests a completely new way of thinking about immunity to pneumococcal diseases, bringing transmission of the pathogen and asymptomatic colonization, the reservoir for such transmission, to the foreground as the essential target for protection. This is what the PneumoCarr project addresses. It seeks a more comprehensive and more quantitative understanding of the colonization process than available until now, and provides a general model of colonization.