The immunological mechanisms that control pneumococcal carriage

Abstract

Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV) in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.

Fig 1. Immunological mechanisms of control of pneumococcal carriage.

The serotype-dependent and -independent immunological mechanisms that control pneumococcal carriage are depicted. Memory B cells and plasma cells specific to capsule and proteins produce IgG. This can lead to antibody-mediated pneumococcal agglutination and antibody-mediated phagocytosis by neutrophils, monocytes, and macrophages. Moreover, IL-17A produced by memory CD4⁺ T cells might lead to recruitment and activation of neutrophils and monocytes/macrophages, thus increasing phagocytosis. CCL2, C-C motif chemokine ligand 2; CD4⁺, cluster of differentiation 4; IgG, immunoglobulin G; IL-17A, interleukin 17-A.