Evaluation of a Vaccine Formulation against Streptococcus pneumoniae Based on Choline-Binding Proteins

Abstract

dStreptococcus pneumoniae has proteins that are attached to its surface by binding to phosphorylcholine of teichoic and lipoteichoic acids. These proteins are known as choline-binding proteins (CBPs). CBPs are an interesting alternative for the development of a cost-effective vaccine, and PspA (pneumococcal surface protein A) is believed to be the most important protective component among the different CBPs. We sought to use CBPs eluted from pneumococci as an experimental vaccine. Since PspA shows variability between isolates, we constructed strains producing different PspAs. We used the nonencapsulated Rx1 strain, which produces PspA from clade 2 (PspA2), to generate a pspA-knockout strain (Rx1 ⌬pspA) and strains expressing PspA from clade 1 (Rx1 pspA1) and clade 4 (Rx1 pspA4). We grew Rx1, Rx1 ⌬pspA, Rx1 pspA1, and Rx1 pspA4 in Todd-Hewitt medium containing 0.5% yeast extract and washed cells in 2% choline chloride (CC). SDS-PAGE analysis of the proteins recovered by a CC wash showed few bands, and the CBPs PspA and PspC (pneumococcal surface protein C) were identified by mass spectrometry analysis. Subcutaneous immunization of mice with these full-length native proteins without adjuvant led to significantly higher rates of survival than immunization with diluent after an intranasal lethal challenge with two pneumococcal strains and also after a colonization challenge with one strain. Importantly, immunization with recombinant PspA4 (rPspA4) without adjuvant did not elicit significant protection.

Chimeric Protein PSPF, a Potential Vaccine for Prevention Streptococcus pneumoniae Infection

“…On the other hand, implementation of the number of separate proteins and adjuvants in vaccine combination makes the vaccine а lot more difficult for standardization and it increases the cost. Major advantage of chimeric protein vaccine beside the cost effectiveness is their simplicity of production and its control, relatively high degree of conservation and T -dependent type of immune memory response [37][38][39]. These considerations resulted in construction and experimental testing of a new recombinant chimeric immunogenic protein PSPF comprising fragments of pneumococcal conservative proteins PspA, Spr1875, PsaA and flagellin domains (FliC).…”

A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis of Streptococcus pneumoniae

“…The αHD of PspA has several properties that make it attractive as a vaccine protein candidate including high expression of the protein at important anatomical sites for colonization and transmission ( D'Mello et al., 2020 ), immunogenicity and cross-reactivity of elicited antibodies ( Nabors et al., 2000 ), accessibility for antibody binding at the cell surface ( Vadesilho et al., 2014 ; Scott et al., 2021 ), and demonstrated protection in animal models of severe infection ( Hollingshead et al., 2000 ; Miyaji et al., 2015 ). The PRD of PspA has also been shown to elicit an antibody response and protection against Spn infection ( Mukerji et al., 2018 ).…”

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

“…The epitope-based pneumococcal vaccines are the last generation of vaccines that are in the pipeline [2]. In this context, pneumococcal surface https://doi.org/10.1016/j.mcp.2019.101446 Received 10 August 2019; Received in revised form 6 September 2019; Accepted 10 September 2019 protein A (PspA) that is located on the surface of bacteria, and choline binding protein A (CbpA), as the most crucial protective surface antigens, have been introduced as vaccine candidate [6]. Another important vaccine candidate is pneumococcal histidine triad (Pht) protein family, including PhtE and PhtD as the conserved member of Pht expressed in pneumococcal pathogenesis [7].…”