T Cell–Mediated Humoral Immune Responses to Type 3 Capsular Polysaccharide of Streptococcus pneumoniae

Abstract

Most pathogenic bacteria express surface carbohydrates called capsular polysaccharides (CPSs). CPSs are important vaccine targets since they are easily accessible and recognizable by the immune system. However, CPS-specific adaptive humoral immune responses can only be achieved by the covalent conjugation of CPSs with carrier proteins to produce glycoconjugate vaccines. We previously described a mechanism by which a model glycoconjugate vaccine can activate the adaptive immune system and demonstrated that the mammalian CD4+ T cell repertoire contains a population of carbohydrate-specific T cells (i.e., Tcarbs). In this study, we employ glycoconjugates of type 3 Streptococcus pneumoniae CPS (Pn3P) to assess whether the carbohydrate-specific adaptive immune response exemplified in our previous study can be applied to the conjugates of this lethal pathogen. Here, we provide evidence for the functional roles of Pn3P-specific CD4+ T cells utilizing mouse immunization schemes that induce Pn3P-specific immunoglobulin G (IgG) responses in a Tcarb-dependent manner.

Polysaccharide structure dictates mechanism of adaptive immune response to glycoconjugate vaccines

“…These findings suggested that Tcarbs contribute to the protection induced by the GBSIII glycoconjugate vaccine. Similar mechanisms involving Tcarb responses were recently reported for type 3 S. pneumoniae glycoconjugates (6).…”

“…1A). As reported with GBSIII and Pn3P (5,6), this result supports a Tcarbdependent mechanism for all three of these glycoconjugates.…”

“…We showed that antigenic fragments of the polysaccharide are presented on the surface by MHCII molecules in the context of a covalently linked peptide from the carrier (5). These surface-presented CPSs are able to activate a subset of CD4 + T cells, designated carbohydratespecific T cells (Tcarbs), which regulate the adaptive immune response to the GBSIII glycoconjugate (5)(6)(7)(8). Similar mechanisms have now been shown to be responsible for T helper responses to glycoconjugates made with the type 3 S. pneumoniae polysaccharide (Pn3P) (6).…”

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

“…36 This leads to poorly-characterized, heterogeneous, and variably immunogenic conjugate vaccines, 37 , 38 Recently, a mechanism for conjugate vaccine-triggered immune response has been proposed. 39 , 40 In this model, uptake and processing of conjugate vaccines by an antigen-presenting cell yield the presentation of a carbohydrate epitope via the major histocompatibility complex class II. This in turn stimulates carbohydrate specific T-cells (Tcarbs) and leads to the production of high-affinity carbohydrate specific IgGs.…”

“…39 , 41 , 42 Considering the mechanism of action in producing conjugate vaccines will help produce knowledge-based vaccines that are target specific, structurally better-defined, both immunogenic and protective, and produced at a much lower cost. 40 This will allow for use on a more global scale to help control pneumococcal infections. Additionally, this will aid in designing vaccines targeted specifically for certain at-risk groups, as it is becoming increasingly clear that vaccination, particularly in adults, is not a one-size-fits-all concept.…”