The host immune dynamics of pneumococcal colonization: implications for novel vaccine development

Abstract

The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines.

Keywords: IPDs, invasive pneumococcal diseases; MHC, major histocompatibility complex; NP, nasopharynx; OPAs, opsonophagocytic antibodies; PPS, pneumococcal polysaccharides; PPVs, pneumococcal polysaccharide vaccines; PcpA, pneumococcal choline-binding protein A; Streptococcus pneumoniae; T cells; WCV, whole cell vaccine; colonization; immunity; vaccines.

Figure 1.

Differential innate recruitment and clearance of pneumococcal carriage in primary vs secondary carriage in mouse colonization model: role of antibodies and CD4 T cells in the clearance.