Immunogenicity and protective efficacy of recombinant alkaline shock protein 23 from Staphylococcus aureus in a murine model

Abstract

The diversity and severity of infections caused and the rapid emergence of antibiotic resistance necessitates the development of a vaccine against Staphylococcus aureus. None of the antigens tried as vaccine candidates so far has been translated into a clinically viable vaccine. Recent research data suggest that antigens with the potential to activate cell mediated immunity along with humoral immunity would be the key to the development of a vaccine. Alkaline shock protein 23, a membrane-anchored protein involved in the stress response, has been identified as a CD4+ T cell antigen from S. aureus. In the present study, we report the evaluation of immunogenicity and protective efficacy of a recombinant alkaline shock protein 23 from S. aureus in mouse models. The gene coding for the protein was cloned and expressed in Escherichia coli, purified using immobilized metal iron affinity chromatography, sequence-confirmed using mass spectrometry and intraperitoneally administered to BALB/c mice. Serum titers of IgG, IgG1, and IgG2a in response to the protein were measured on post-immunization days 21, 35 and 42 using indirect ELISA and compared to control mice injected with PBS. Our results showed that the protein induced significantly higher (p < 0.01) antibody responses in immunized mice compared to the control mice. The mean serum antibody titers of IgG, IgG1 and IgG2a three weeks after the last immunization were found to be 25600, 25600 and 12800 respectively. Moreover, we found that immunization with Asp23 protected mice from a lethal dose of S. aureus strain USA300.

Updates on Staphylococcal Vaccines

“…Data from recent studies indicate that the secret to developing a vaccine may lie in finding antigens that can both stimulate humoral immunity and cell-mediated immunity [48]. One of the membrane-anchored proteins involved in the stress response, alkaline shock protein 23, has been identified as an S. aureus CD4+ T cell antigen [48].…”

“…Data from recent studies indicate that the secret to developing a vaccine may lie in finding antigens that can both stimulate humoral immunity and cell-mediated immunity [48]. One of the membrane-anchored proteins involved in the stress response, alkaline shock protein 23, has been identified as an S. aureus CD4+ T cell antigen [48]. On post-immunization days 21, 35, and 42, serum titers of IgG, IgG1, and IgG2a produced in response to the protein were assessed using indirect ELISA and compared to control mice injected with PBS [48].…”

“…One of the membrane-anchored proteins involved in the stress response, alkaline shock protein 23, has been identified as an S. aureus CD4+ T cell antigen [48]. On post-immunization days 21, 35, and 42, serum titers of IgG, IgG1, and IgG2a produced in response to the protein were assessed using indirect ELISA and compared to control mice injected with PBS [48]. As compared to the control group, the results indicated that the protein generated much greater antibody responses in vaccinated mice [48].…”

“…Predicting bacterial immunogens is an essential step in the reverse-vaccinology process [56]. Reverse vaccinology is a vaccine-prediction process that uses a genome sequence and the resultant complete proteome repertoire to identify candidates [48]. The entire spectrum of potential antigens is found in microbial genomes, which serve as the data foundation for the creation of vaccines [38].…”

Alantolactone Enhances the Phagocytic Properties of Human Macrophages and Modulates Their Proinflammatory Functions

“…As previously recognized, this bacteria commonly causes nosocomial infections, but some strains have a propensity to disseminate between otherwise healthy individuals, giving rise to community-acquired illnesses ( Mediavilla et al., 2012 ). The most serious concern occurred with the emergence of multi-drug resistant strains, such as methicillin-resistant S. aureus (MRSA) demonstrating enhanced infectivity and virulence ( Nimmo, 2012 ; Francis and Kuyyalil, 2018 ). Incredibly, these bacteria can colonize every tissue, causing pathologies varying from whole range of skin and soft tissue infections to fatal invasive diseases, such as necrotizing pneumonia and sepsis ( Gonzalez et al., 2005 ; Labandeira-Rey et al., 2007 ; Saavedra-Lozano et al., 2008 ).…”