Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

Chen, Qing; Li, Cai Hong; Wang, Xiu Rong; Zeng, Rui; Yin, Xiao; Feng, Hui Dong; Wei, Lin

doi:10.1038/cmi.2009.10

Cited by 17 publications

(14 citation statements)

References 15 publications

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“…A number of non-M-protein antigens have also been characterized as GAS vaccine candidates, although none of these have reached human clinical trials. Non-M-protein antigens that have been tested in animal models include fibronectin binding protein A (FbaA) (564) (579), and trigger factor (TF) (579). While each of these antigens exhibited protection against GAS infection in selected animal models, there are concerns regarding the incorporation of a number of these antigens into GAS vaccine preparations.…”

Section: Other Vaccine Targetsmentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

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SUMMARY Streptococcus pyogenes , also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.

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Section: Other Vaccine Targetsmentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

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“…There is ample evidence that Abs develop after exposure to GAS bacteria (7)(8)(9)(10)(11) and that Abs have protective capacity (12)(13)(14)(15)(16)(17). Consequently, vaccine development has focused on Abs and to a lesser extent on cellular T cell-based immunity.…”

mentioning

confidence: 99%

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children

Mortensen

Nissen

Blauenfeldt

et al. 2015

The Journal of Immunology

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Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted protein. The response primarily consisted of three subsets of Th1 T cells, in which the TNF-α+ and IL-2+TNF-α+ subsets were most frequent. Humoral immunity was dominated by IgG1 and IgG3, whereas the Th2-associated IgG4 isotype was only detected at very low amounts. IgG3 levels correlated significantly with IFN-γ, but not with IL-5, IL-13, IL-17, or TNF-α. Interestingly, children showed a similar pattern of Ag-specific cytokine release, but displayed significantly lower levels of IgG3 and IFN-γ compared with adults. Thus, human immune responses against S. pyogenes consist of a robust Th1 cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.

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“…The fba gene was reported in M1, M2, M4, M22, M28 and M49 GAS, but was not detected in other serotypes . Intraperitoneal immunization of BALB/c mice with FbaA/CFA produced an elevated humoral IgG response similar to that of M protein and conferred a level of protection on par with M1 protein following homologous (M1) intraperitoneal challenge (Ma et al 2009). …”

Section: Fibronectin-binding Protein Amentioning

confidence: 98%

“…The protective efficacy of subcutaneous immunization with group A carbohydrate (CHO) and streptococcal secreted esterase (Sse) adsorbed to Alum was determined by survival of lethal challenge (Sabharwal et al 2006;Liu et al 2007). Most frequently, protective efficacy against systemic GAS infection is measured by survival against a lethal dose of GAS (Brandt et al 2000;Gillen et al 2008;Okamoto et al 2005;McMillan et al 2004;Sanderson-Smith et al 2006;Kapur et al 1994;Courtney et al 2003;Ma et al 2009;Terao et al 2005;Schulze et al 2006) or by measuring dissemination of GAS to organs (Turner et al 2009;McArthur et al 2004).…”

Section: Protective Efficacy Studiesmentioning

confidence: 99%

“…In both cases advancement to clinical trials was based upon the success of the vaccines in eliciting systemic immunity in mouse models. Most murine models to evaluate systemic immunity in response to GAS antigens have utilized subcutaneous (Brandt et al 2000;Sabharwal et al 2006;Okamoto et al 2005;McMillan et al 2004;Kapur et al 1994;Liu et al 2007;Kawabata et al 2001;Ma et al 2009;Terao et al 2005) and less frequently intraperitoneal (Henningham et al 2012;Guzmán et al 1999), intramuscular (Ulrich 2008;Turner et al 2009), or intravenous (Gillen et al 2008;Courtney et al 2003) immunization in the presence of CFA/incomplete Freund's adjuvant (IFA). CFA is an efficient stimulator of cellmediated immunity and augments the humoral immune response, however, CFA is banned for use in humans due to toxic side effects so it can be difficult to translate the results of these studies to humans [reviewed in Lindblad 2000].…”

Section: Protective Efficacy Studiesmentioning

confidence: 99%

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Group A Streptococcal Vaccine Candidates: Potential for the Development of a Human Vaccine

Henningham

Gillen

Walker

2012

Host-Pathogen Interactions in Streptococcal Diseases

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Currently there is no commercial Group A Streptococcus (GAS; S. pyogenes) vaccine available. The development of safe GAS vaccines is challenging, researchers are confronted with obstacles such as the occurrence of many unique serotypes (there are greater than 150 M types), antigenic variation within the same serotype, large variations in the geographical distribution of serotypes, and the production of antibodies cross-reactive with human tissue which can lead to host auto-immune disease. Cell wall anchored, cell membrane associated, secreted and anchorless proteins have all been targeted as GAS vaccine candidates. As GAS is an exclusively human pathogen, the quest for an efficacious vaccine is further complicated by the lack of an animal model which mimics human disease and can be consistently and reproducibly colonized by multiple GAS strains.

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Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

Cited by 17 publications

References 15 publications

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children

Group A Streptococcal Vaccine Candidates: Potential for the Development of a Human Vaccine

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