Put more succinctly, if there is no carriage, there is no disease. VE-col is thus a biologically appropriate surrogate marker for vaccine effect on mucosal and invasive pneumococcal disease at the individual level. This derives from the fact that NP carriage is a necessary, sequentially close precursor to pneumococcal disease. As pneumococcal NP carriage is
the reservoir for transmission in a community, vaccine-induced buy PD-0332991 reduction in VT carriage among vaccinated children has resulted in decreased VT carriage and disease among larger segments of the population. The magnitude of this indirect effect can surpass the direct effects of PCV on the absolute number of pneumococcal disease cases averted. National regulatory agencies are primarily concerned with the direct benefits of the reduction in NP carriage translating to
a reduction in an individual’s risk of disease. NP carriage data may be supplementary or more useful post-licensure for surveillance of serotype replacement and ongoing safety monitoring. In the regulatory pathway, the consideration of indirect, population-level effects in licensure decisions is a paradigm shift and merits more formal discussion and consensus-building. For different types of pneumococcal vaccine products, the relative importance Antiinfection Compound Library ic50 of NP carriage in licensure decisions may vary. For new PCVs, the path of licensure using immunological criteria is well-established, and NP carriage data could be considered less important. However, when considering conjugate-protein vaccine combinations or novel-mechanism vaccines such as protein vaccines, the importance of considering NP carriage data, VE-col, in licensure decisions is increased. Since protein candidates act through different mechanisms,
it will be difficult to have specific, comparable immunological correlates for each one. Areas for further from research The immunological correlates for pneumonia and mucosal immune protection are not established and warrant further study. The pathophysiology of certain invasive serotypes that are rarely carried but important causes of invasive disease – such as 1, 5 and 7 – need to be further elucidated to help explain the factors relating VE-col to VE-disease for these serotypes. Further research is needed on the mechanism of action of protein vaccines on NP carriage as well as vaccine impact on density of colonization. As NP sampling methods can better quantify density of colonization, the link between density and risk of extension to mucosal or invasive disease can be better described for various serotypes. The discussion of NP carriage in licensure and public Modulators health decisions could be furthered by convening an expert meeting to review existing WHO guidelines for the development of pneumococcal vaccines.