eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
Current issue Archive Manuscripts accepted About the journal Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank

vol. 43
Experimental immunology

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

Dileep Francis, Surekha Kuyyalil

(Centr Eur J Immunol 2018; 43 (4): 371-377)
Online publish date: 2018/12/31
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
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.

Asp23, Staphylococcus aureus, CD4+ T cell antigen, vaccine

Lowy FD (1998): Staphylococcus aureus infections. N Engl J Med 339: 520-532.
Chambers HF (2005): Community-associated MRSA – resistance and virulence converge. N Engl J Med 352: 1485-1487.
Chambers HF, Deleo FR (2009): Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7: 629-641.
Proctor RA (2012): Is there a future for a Staphylococcus aureus vaccine? Vaccine 30: 2921-2927.
Thomsen I, Dudney H, Creech CB (2010): Searching for the holy grail of a staphylococcal vaccine. Hum Vaccin 6: 1068-1070.
Schaffer AC, Lee JC (2008): Vaccination and passive immunisation against Staphylococcus aureus. Int J Antimicrob Agents 32 Suppl 1: S71-78.
Fowler VG, Proctor RA (2014): Where does a Staphylococcus aureus vaccine stand? Clin Microbiol Infect 20: 66-75.
Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004): Interferon-: an overview of signals, mechanisms and functions. J Leukoc Biol 75: 163-189.
Ye P, Rodriguez FH, Kanaly S, et al. (2001): Requirement of interleukin 17 receptor signaling for lung Cxc chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194: 519-528.
Verkaik NJ, Boelens HA, Vogel CP de, et al. (2010): Heterogeneity of the humoral immune response following Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 29: 509-518.
Kolata J, Bode LGM, Holtfreter S, et al. (2011): Distinctive patterns in the human antibody response to Staphylococcus aureus bacteremia in carriers and non-carriers. Proteomics 11: 3914-3927.
Laupland KB, Ross T, Gregson DB (2008): Staphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006. J Infect Dis 198: 336-343.
Litjens NHR, Huisman M, van den Dorpel M, Betjes MGH (2008): Impaired immune responses and antigen-specific memory CD4+ T cells in hemodialysis patients. J Am Soc Nephrol 19: 1483-1490.
Wiese L, Mejer N, Schønheyder HC, et al. (2013): A nationwide study of comorbidity and risk of reinfection after Staphylococcus aureus bacteraemia. J Infect 67: 199-205.
Joshi A, Pancari G, Cope L, et al. (2012): Immunization with Staphylococcus aureus iron regulated surface determinant B (IsdB) confers protection via Th17/IL17 pathway in a murine sepsis model. Hum Vaccin Immunother 8: 336-346.
Lawrence PK, Rokbi B, Arnaud-Barbe N, et al. (2012): CD4 T cell antigens from Staphylococcus aureus Newman strain identified following immunization with heat-killed bacteria. Clin Vaccine Immunol 19: 477-489.
Kuroda M, Ohta T, Hayashi H (1995): Isolation and the gene cloning of an alkaline shock protein in methicillin resistant Staphylococcus aureus. Biochem Biophys Res Commun 207: 978-984.
Gertz S, Engelmann S, Schmid R, et al. (1999): Regulation of  B-dependent transcription of sigB and asp23 in two different Staphylococcus aureus strains. Mol Gen Genet 261: 558-566.
Kullik I, Giachino P, Fuchs T (1998): Deletion of the alternative sigma factor  β in Staphylococcus aureus reveals its function as a global regulator of virulence genes. J Bacteriol 180: 4814-4820.
Maass S, Sievers S, Zühlke D, et al. (2011): Efficient, global-scale quantification of absolute protein amounts by integration of targeted mass spectrometry and two-dimensional gel-based proteomics. Anal Chem 83: 2677-2684.
Muller M, Reiß S, Schlüter R, et al. (2014): Deletion of membrane-associated Asp23 leads to upregulation of cell wall stress genes in Staphylococcus aureus. Mol Microbiol 93: 1259-1268.
David MZ, Daum RS (2010): Community-associated methicillin-resistant staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23: 616-687.
Jansen KU, Girgenti DQ, Scully IL, Anderson AS (2013): Vaccine review: Staphyloccocus aureus vaccines: Problems and prospects. Vaccine 31: 2723-2730.
Fattom AI, Sarwar J, Ortiz A, Naso R (1996): A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge. Infect Immun 64: 1659-1665.
Josefsson E, Hartford O, O’Brien L, et al. (2001): Protection against experimental Staphylococcus aureus arthritis by vaccination with clumping factor A, a novel virulence determinant. J Infect Dis 184: 1572-1580.
Vernachio J, Bayer AS, Le T, et al. (2003): Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis. Antimicrob. Agents Chemother 47: 3400-3406.
Josefsson E, Higgins J, Foster TJ, Tarkowski A (2008): Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence. PLoS One 3: e2206.
Kuklin NA, Clark DJ, Secore S, et al. (2006): A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model. Infect Immun 74: 2215-2223.
Lowy FD (1998): Staphylococcus aureus infections. N Engl J Med 339: 520-532.
Leveen HH, Falk G, Borek B, et al. (1973). Chemical acidification of wounds. An adjuvant to healing and the unfavorable action of alkalinity and ammonia. Ann Surg 178: 745-753.
Jansen WT, Hogenboom S, Thijssen MJ, et al. (2001): Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice. Infect Immun 69: 787-793.
Berger A (2000): Th1 and Th2 responses: what are they? BMJ 321: 424.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe