scholarly journals Clinical and Microbiological Responses of Volunteers to Combined Intranasal and Oral Inoculation with a Streptococcus gordonii Carrier Strain Intended for Future Use as a Group A Streptococcus Vaccine

2005 ◽  
Vol 73 (4) ◽  
pp. 2360-2366 ◽  
Author(s):  
Karen L. Kotloff ◽  
Steven S. Wasserman ◽  
Kevin F. Jones ◽  
Sofie Livio ◽  
Dennis E. Hruby ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Group A Streptococcus ◽  
Nasal Congestion ◽  
Vaccine Vector ◽  
Mucosal Vaccine ◽  
Respiratory Pathogens ◽  
Streptococcus Gordonii ◽  
Protein Antigens ◽  
Oral Inoculation ◽  
Group A

ABSTRACT Streptococcus gordonii shows promise as a live mucosal vaccine vector for immunization against respiratory pathogens. In preparation for clinical trials to evaluate S. gordonii engineered to express group A streptococcal M protein antigens, we characterized the responses of 150 healthy volunteers to combined nasal and oral inoculation with approximately 1.5 × 109 CFU of SP204(1-1), an S. gordonii strain not bearing vaccine antigens. SP204(1-1) was selected for resistance to streptomycin and 5-fluoro-2-deoxyuridine to distinguish it from indigenous flora. In two antibiotic treatment studies, we performed serial culturing of nose, mouth, and saliva samples from 120 subjects treated with azithromycin beginning 5 days after inoculation to determine whether SP204(1-1) could be rapidly eliminated should safety concerns arise. A natural history study was performed to assess the time until spontaneous eradication in the remaining 30 subjects, who did not receive the antibiotic and who were monitored with repeated culturing for 14 weeks after inoculation. SP204(1-1) was generally well tolerated. Symptoms reported most often within 5 days of inoculation were nasal congestion (36%), headache (30%), and sore throat (19%). The strain was detected by culturing in 98% of subjects. A single dose of azithromycin eliminated colonization in 95% of subjects; all subjects receiving a 5-day course of an antibiotic showed clearance by day 11. Without the antibiotic, 82% of subjects showed spontaneous eradication of the implanted strain within 7 days, and all showed clearance by 35 days. The results of these clinical trials provide encouragement that the use of S. gordonii as a live mucosal vaccine vector is a feasible strategy.

scholarly journals Multicomponent Vaccines against Group A Streptococcus Can Effectively Target Broad Disease Presentations

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1025
Author(s):  
Helen A. Shaw ◽  
James Ozanne ◽  
Keira Burns ◽  
Fatme Mawas
Keyword(s):  
Immune Response ◽  
Group A Streptococcus ◽  
Specific Antigen ◽  
Binding Activity ◽  
Protein Antigens ◽  
Wide Range ◽  
Antibody Titres ◽  
Functional Immunity ◽  
Group A ◽  
Rheumatic Heart

Group A Streptococcus (GAS) is an important global human pathogen, with a wide range of disease presentations, from mild mucosal infections like pharyngitis to invasive diseases such as toxic shock syndrome. The effect on health and mortality from GAS infections is substantial worldwide, particularly from autoimmune sequelae-like rheumatic heart disease (RHD), and there is currently no licenced vaccine. We investigated protein antigens targeting a broad range of GAS disease presentations as vaccine components in individual and combination formulations. The potency and functional immunity generated were evaluated and compared between groups. Antibodies against all components were found in pooled human IgG (IVIG) and an immune response generated following the subcutaneous immunisation of mice. A combination immunisation showed a reduction in IgG response for SpyCEP but an increase for Cpa and Mac-1 (IdeS). An opsonophagocytosis assay (OPA) showed the killing of GAS with immune sera against M protein and combination groups, with a lower killing activity observed for immune sera against other individual antigens. Specific antigen assays showed functional immunity against SpyCEP and Mac-1 from both individual and combination immunisations, with the activity correlating with antibody titres. However, efficient blocking of the binding activity of Cpa to collagen I and fibronectin could not be demonstrated with immune sera or purified IgG. Our data indicate that combination immunisations, while effective at covering a broader range of virulence factors, can also affect the immune response generated. Further, our results showed that an OPA alone is inadequate for understanding protection from vaccination, particularly when considering protection from immune evasion factors and evaluation of the colonisation leading to pharyngitis.

scholarly journals Correlation Between Immunoglobulin Dose Administered and Plasma Neutralization of Streptococcal Superantigens in Patients With Necrotizing Soft Tissue Infections

2020 ◽  
Vol 71 (7) ◽  
pp. 1772-1775 ◽  
Author(s):  
Helena Bergsten ◽  
Martin Bruun Madsen ◽  
Francois Bergey ◽  
Ole Hyldegaard ◽  
Steinar Skrede ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Clinical Trials ◽  
T Cell ◽  
Soft Tissue ◽  
Negative Correlation ◽  
Group A Streptococcus ◽  
T Cell Proliferation ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Group A

Abstract Analyses of plasma collected pre- and postadministration of intravenous immunoglobulin (IVIG) from patients with group A Streptococcus necrotizing soft tissue infections demonstrated a negative correlation between IVIG dose and toxin-triggered T-cell proliferation (r = −.67, P < .0001). One 25-g IVIG dose was sufficient to yield plasma-neutralizing activity against streptococcal superantigens. Clinical Trials Registration. NCT 01790698 and NCT02111161.

scholarly journals Rational Design of a Glycoconjugate Vaccine against Group A Streptococcus

2020 ◽  
Vol 21 (22) ◽  
pp. 8558
Author(s):  
Roberta Di Benedetto ◽  
Francesca Mancini ◽  
Martina Carducci ◽  
Gianmarco Gasperini ◽  
Danilo Gomes Moriel ◽  
...  
Keyword(s):  
Rational Design ◽  
Negative Impact ◽  
Group A Streptococcus ◽  
Protein Antigens ◽  
Hemolysis Assay ◽  
Middle Income ◽  
Middle Income Countries ◽  
Streptolysin O ◽  
Group A ◽  
Improved Design

No commercial vaccine is yet available against Group A Streptococcus (GAS), major cause of pharyngitis and impetigo, with a high frequency of serious sequelae in low- and middle-income countries. Group A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive vaccine candidate. Here, we explored the possibility to use GAS Streptolysin O (SLO), SpyCEP and SpyAD protein antigens with dual role of antigen and carrier, to enhance the efficacy of the final vaccine and reduce its complexity. All protein antigens resulted good carrier for GAC, inducing similar anti-GAC IgG response to the more traditional CRM197 conjugate in mice. However, conjugation to the polysaccharide had a negative impact on the anti-protein responses, especially in terms of functionality as evaluated by an IL-8 cleavage assay for SpyCEP and a hemolysis assay for SLO. After selecting CRM197 as carrier, optimal conditions for its conjugation to GAC were identified through a Design of Experiment approach, improving process robustness and yield This work supports the development of a vaccine against GAS and shows how novel statistical tools and recent advancements in the field of conjugation can lead to improved design of glycoconjugate vaccines.

Moving forward: a mucosal vaccine against group A streptococcus

2009 ◽  
Vol 8 (6) ◽  
pp. 747-760 ◽  
Author(s):  
Melina M Georgousakis ◽  
David J McMillan ◽  
Michael R Batzloff ◽  
Kadaba S Sriprakash
Keyword(s):  
Group A Streptococcus ◽  
Mucosal Vaccine ◽  
Group A

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

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