Pneumococcal Surface Proteins as Virulence Factors, Immunogens, and Conserved Vaccine Targets

Abstract

Streptococcus pneumoniae is an opportunistic pathogen that causes over 1 million deaths annually despite the availability of several multivalent pneumococcal conjugate vaccines (PCVs). Due to the limitations surrounding PCVs along with an evolutionary rise in antibiotic-resistant and unencapsulated strains, conserved immunogenic proteins as vaccine targets continue to be an important field of study for pneumococcal disease prevention. In this review, we provide an overview of multiple classes of conserved surface proteins that have been studied for their contribution to pneumococcal virulence. Furthermore, we discuss the immune responses observed in response to these proteins and their promise as vaccine targets.

Keywords: CbpA; PhtD pneumococcal histidine triad protein D; PspA; PsrP; Streptoccoccus pneumoniae; conjugate vaccine; pneumococcal protein vaccine; pneumolysin (PLY).

Figure 1

Interactions of pneumococcal factors representative of classes within the host respiratory epithelium. (A) PLY is released from Spn. It is pro-inflammatory in the environment and PLY monomers aggregate to form ring complexes that can trigger host cell death. It can interact with MRC-1 to promote bacterial survival. (B) CBPs impair complement-mediated killing by the host. PcpA influences biofilm formation and pneumococcal adhesion. CbpA binds its main receptor, pIgR, to promote adherence. PspA binds lactoferrin for critical iron uptake for the bacterium from the host and inhibits apolactoferrin. Both CbpA and PspA can bind lactate dehydrogenase to enhance virulence. (C) The PHTs are well-conserved surface proteins on the pneumococcus and maintain metal homeostasis through Zn and Ni binding. (D) A model showing PsrP’s SRR1-BR region extending past the CPS. While the SRR1 glycans potentially interact with another host ligand (1), the basic region binds Keratin-10 (2). Alternatively, as previously hypothesized, the glycans may be employed as important interactors with the CPS to hoist PsrP up so that it can extend past the capsule (3).