Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Infect Immun ; 73(4): 2360-6, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15784582

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 x 10(9) 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.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Outer Membrane Proteins/immunology , Carrier Proteins/immunology , Streptococcal Vaccines/immunology , Streptococcus pyogenes/immunology , Streptococcus/genetics , Vaccines, Synthetic/immunology , Administration, Intranasal , Administration, Oral , Adolescent , Adult , Antigens, Bacterial/genetics , Azithromycin/pharmacology , Bacterial Outer Membrane Proteins/genetics , Carrier Proteins/genetics , Humans , Streptococcal Vaccines/administration & dosage , Streptococcus/drug effects , Vaccines, Synthetic/administration & dosage
2.
Infect Immun ; 70(5): 2487-91, 2002 May.
Article in English | MEDLINE | ID: mdl-11953386

ABSTRACT

Several key protein structural attributes were altered in an effort to optimize expression and immunogenicity of a foreign protein (M protein from Streptococcus pyogenes) exposed on the surface of Streptococcus gordonii commensal bacterial vectors: (i) a shorter N-terminal region, (ii) the addition of a 94-amino-acid spacer, and (iii) the addition of extra C-repeat regions (CRR) from the M6 protein. A decrease in the amount of cell surface M6 was observed upon deletion of 10 or more amino acid residues at the N terminus. On the other hand, reactivity of monoclonal antibody to surface M6 increased with the addition of the spacer adjacent to the proline- and glycine-rich region, and an increase in epitope dosage was obtained by adding another CRR immediately downstream of the original CRR. The results obtained should facilitate the design of improved vaccine candidates using this antigen delivery technology.


Subject(s)
Antigens, Bacterial , Bacterial Outer Membrane Proteins/biosynthesis , Carrier Proteins/biosynthesis , Genetic Vectors , Recombinant Proteins/biosynthesis , Streptococcus/genetics , Streptococcus/immunology , Amino Acid Sequence , Animals , Antibodies, Bacterial/blood , Bacterial Outer Membrane Proteins/chemistry , Bacterial Outer Membrane Proteins/immunology , Carrier Proteins/chemistry , Carrier Proteins/immunology , Immunoglobulin G/blood , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Recombinant Proteins/immunology , Repetitive Sequences, Amino Acid
SELECTION OF CITATIONS
SEARCH DETAIL
...