Vaccination equally enables both genetically susceptible and resistant mice to control infection with group A streptococci

Siegert, Jeannette; Sastalla, Inka; Chhatwal, Gursharan S.; Medina, Eva

doi:10.1016/j.micinf.2005.06.024

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…It has been reported that efficient protection after vaccination could only be acquired by elicitation of high level of long-lasting anti-GAS specific antibodies [19]. Polyclonal antisera raised against heat killed GAS was capable of transferring passive protection which was dependent on the amount of anti-GAS antibodies present in the immune serum and the time of administration post-infection.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

2009

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Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4+ and CD8+ T-cell subsets confirmed that an active de novo immune response, involving CD4+ T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4+ T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease.

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Section: Discussionmentioning

confidence: 99%

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

2009

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“…Immunization procedures were performed as previously described (5). Briefly, 10-week-old male CD-1 mice (Charles River Laboratories) were injected intraperitoneally with 2 × 10 6 to 4 × 10 6 CFU heat-killed WT M1T1 GAS in PBS on days 0, 7, and 14.…”

Section: Methodsmentioning

confidence: 99%

“…Because preventative vaccines against GAS infections are not currently available, the immune response of the human host is a major determinant of disease outcome. The human host can develop adaptive immunity to GAS (3, 4), and anti-GAS antibodies (5), including those introduced by intravenous immunoglobulin treatment (6), can promote opsonophagocytosis and aid in the resolution of infection. Although GAS organisms in the bloodstream are particularly susceptible to antibody binding, which promotes opsonophagocytosis (7), many GAS strains with invasive potential have evolved strategies to counteract phagocyte clearance mechanisms that normally prevent bacterial dissemination (8–10).…”

Section: Introductionmentioning

confidence: 99%

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Okumura

Anderson

Döhrmann

et al. 2013

mBio

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The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.

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“…For generation of high-titered immune sera for use as a positive control in OPK assays, mice were immunized intraperitoneally with 10 7 CFU of heat-killed GAS 88/30 strain (serotype M97). 34 All immunizations were performed on days 0, 21 and 42. Blood samples were collected on days -1, 20, 41 and 50.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity in mice and non-human primates of the Group A Streptococcal J8 peptide vaccine candidate conjugated to CRM197

Caro-Aguilar

Ottinger

Hepler

et al. 2013

Human Vaccines & Immunotherapeutics

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Vaccination equally enables both genetically susceptible and resistant mice to control infection with group A streptococci

Cited by 8 publications

References 31 publications

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Immunogenicity in mice and non-human primates of the Group A Streptococcal J8 peptide vaccine candidate conjugated to CRM197

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