CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Lawrence, Paulraj K.; Rokbi, Bachra; Arnaud-Barbe, Nadège; Sutten, Eric L.; Norimine, Junzo; Lahmers, Kevin K.; Brown, Wendy C.

doi:10.1128/cvi.05642-11

Cited by 18 publications

(21 citation statements)

References 95 publications

(94 reference statements)

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“…Hence, BME extract comprising most exoproteins of the biofilm matrix may ensure that not only different areas of the biofilm but also various cell types present within the biofilm are targeted. It is important to note that vaccinations with other multicomponent extracts, such as a heat-killed or a PLKE, which have been shown to provide protection against S. aureus infections (41,61,62), were less efficient than BME in reducing the number of bacteria inside a biofilm, using a mesh-associated biofilm infection model. The reason behind the low efficiency of heat-killed and PLKEs might be that they probably do not include biofilm-specific antigens like the BME extract (Fig.…”

Section: Discussionmentioning

confidence: 99%

Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

et al. 2014

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The Staphylococcus aureus biofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation of S. aureus biofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response against S. aureus infections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and proteinbased biofilm matrices produced by two clinical S. aureus strains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing of S. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using an in vivo model of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine against S. aureus biofilm-associated infections.

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Section: Discussionmentioning

confidence: 99%

Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

et al. 2014

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“…However, the numbers of CD4 ϩ and CD8 ϩ T cells did not differ significantly between groups B and D or between groups C and D. In general, CD4 ϩ (Th1 and Th2) T-helper cells activate opsonic IgG antibodies and cell-mediated immune responses, and cytotoxic CD8 ϩ T cells destroy the intracellular bacterial pathogens (36,37). It has previously been suggested that CD4 ϩ T cells are essential for the S. aureus vaccine to be effective (38). Moreover, the S. aureus envelope component of PA-immunized animals elicited higher levels of CD4 ϩ and CD8 ϩ T cells than that of control animals (39).…”

Section: Resultsmentioning

confidence: 93%

Generation of a Novel Staphylococcus aureus Ghost Vaccine and Examination of Its Immunogenicity against Virulent Challenge in Rats

Vinod

Park

et al. 2015

Infect Immun

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Staphylococcus aureus is a Gram-positive pathogen that causes a wide range of infections in humans and animals. Bacterial ghosts are nonliving, empty cell envelopes and are well represented as novel vaccine candidates. In this study, we examined the immunogenicity and protective efficacy of S. aureus ghosts (SAGs) against a virulent challenge in rats. Nonliving SAGs were generated by using the MIC of sodium hydroxide. The formation of a transmembrane lysis tunnel structure in SAGs was visualized by scanning electron microscopy. To investigate these SAGs as a vaccine candidate, rats were divided into four groups, A (nonimmunized control), B (orally immunized), C (subcutaneously immunized), and D (intravenously immunized). The IgG antibody responses were significantly stronger in the SAG-immunized groups than in the nonimmunized control group (P < 0.05). Moreover, a significant increase in the populations of CD4 ؉ and CD8 ؉ T cells was observed in all three immunized groups (P < 0.05). We also found that serum bactericidal antibodies were significantly elicited in the SAG-immunized groups (P < 0.05). Most importantly, the bacterial loads in the immunized groups were significantly lower than those in the nonimmunized control group (P < 0.01). These results suggest that immunization with SAGs induces immune responses and provides protection against a virulent S. aureus challenge.

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“…The same thing was reported by Rolph and Kaufmann (2001), Chen et al (2001) and Field et al (2007) which uses a combination of CD40 and vaccine of heat-killed Listeria mononcytogenes and Leishmania major. The development of vaccines based on cell-mediated immunity was also reported by Lawrence et al (2012) in a vaccination using HKSA. It was able to induce cellular immunity, particularly CD4+ T lymphocytes induced by superantigens found in isolates of S. aureus (strain Newman).…”

Section: Vaccination Based On Cell-mediated Immunitymentioning

confidence: 78%

“…While the role and ability of the neutrophils is enhanced by antibodies to kill S. aureus, the antibody alone without the action of the neutrophils, is known to be insufficient to provide protective effects (Jansen et al, 2013). In addition, several studies have developed a vaccine for S. aureus which is able to induce CD8+T cell (Rolph and Kaufmann, 2001) and CD4+ (Lawrence et al, 2012) as the main axis in cellular immunity.…”

Section: Vaccination Based On Cell-mediated Immunitymentioning

confidence: 99%

“…It was able to induce cellular immunity, particularly CD4+ T lymphocytes induced by superantigens found in isolates of S. aureus (strain Newman). The action of CD4+ is urgently needed to promote interferon-gamma (IFN-γ) activities which have functions to mediate B lymphocyte transformation into an active form to produce IgG antibodies and activate phagocytic cells (mononuclear and polymorphonuclear) to eliminate S. aureus (Lawrence et al, 2012).…”

Section: Vaccination Based On Cell-mediated Immunitymentioning

confidence: 99%

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<i>Staphylococcus aureus</i> Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

Sandi¹,

Wanahari²,

MacPhillamy³

et al. 2015

American Journal of Infectious Diseases

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Staphylococcus aureus (S. aureus) is a major cause various infections in humans and animals throughout the world. The increasing incidence of S. aureus infection, particularly methicillin-resistant Staphylococcus aureus (MRSA) is complicated by the antibiotic-resistance phenomenon. Thus, it requires new strategies to prevent wider scale of its incidence occurring. Preventative methods against infectious diseases through vaccination can prevent, control and reduce the severity of the disease process. Various methods have been used in the development of vaccines to prevent S. aureus infections, but no satisfactory results have been obtained. Recent studies suggests that multivalent vaccines based on cell-mediated immunity is expected to provide better protection against infection. The purpose of this article is to summarize the challenges of S. aureus infection and the current status of its potential solution with the development of a multivalent vaccine and to explain the latest approaches recommended to obtain successful development of S. aureus vaccine by inducing T-cells CD8+, CD4+ and Th17. Seven MRSA Indonesian origin isolates from humans and dairy-cattle were used as candidate vaccines as genotypic characterization had previously been performed (coa, eta, etb, hla, hlb, cap5, cap8, fnbA, fnbB and mecA). Vaccination can be performed with live-attenuated or killed-vaccine and could be combined with an injection of αCD40 monoclonal-antibodies (mAbs) with the aim to induce cellular-based active immunity (T CD8+, CD4+ and Th17). These isolates are expected to be safe vaccine candidates with immunogenic-protective properties based on genetic and antigenic variation to prevent and control staphylococcal infections in humans and animals.

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CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

Cited by 18 publications

References 95 publications

Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

Generation of a Novel Staphylococcus aureus Ghost Vaccine and Examination of Its Immunogenicity against Virulent Challenge in Rats

<i>Staphylococcus aureus</i> Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

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