Recombinant PhpA Protein, a Unique Histidine Motif-Containing Protein from Streptococcus pneumoniae, Protects Mice against Intranasal Pneumococcal Challenge

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Published inInfection and Immunity Vol. 69; no. 6; pp. 3827 - 3836
Main Authors YING ZHANG, MASI, Amy W, BARNIAK, Vicki, MOUNTZOUROS, Ken, HOSTETTER, Margaret K, GREEN, Bruce A
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.06.2001
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Abstract Classifications Services IAI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue IAI About IAI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy Connect to IAI IAI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0019-9567 Online ISSN: 1098-5522 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to IAI .asm.org, visit: IAI       
AbstractList The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the current conjugate vaccine may still cause pneumococcal disease. To address these serotypes and the remaining otitis media due to Streptococcus pneumoniae, we have been evaluating antigenically conserved proteins from S. pneumoniae as vaccine candidates. A previous report identified a 20-kDa protein with putative human complement C3-proteolytic activity. By utilizing the publicly released pneumococcal genomic sequences, we found the gene encoding the 20-kDa protein to be part of a putative open reading frame of approximately 2,400 bp. We recombinantly expressed a 79-kDa fragment (rPhpA-79) that contains a repeated HxxHxH motif and evaluated it for vaccine potential. The antibodies elicited by the purified rPhpA-79 protein were cross-reactive to proteins from multiple strains of S. pneumoniae and were against surface-exposed epitopes. Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain. In contrast, immunization with the 20-kDa portion of the PhpA protein did not protect mice. These results suggest that rPhpA-79 is a potential candidate for use as a vaccine against pneumococcal systemic disease and otitis media.
ABSTRACT The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the current conjugate vaccine may still cause pneumococcal disease. To address these serotypes and the remaining otitis media due to Streptococcus pneumoniae , we have been evaluating antigenically conserved proteins from S. pneumoniae as vaccine candidates. A previous report identified a 20-kDa protein with putative human complement C3-proteolytic activity. By utilizing the publicly released pneumococcal genomic sequences, we found the gene encoding the 20-kDa protein to be part of a putative open reading frame of approximately 2,400 bp. We recombinantly expressed a 79-kDa fragment (rPhpA-79) that contains a repeated HxxHxH motif and evaluated it for vaccine potential. The antibodies elicited by the purified rPhpA-79 protein were cross-reactive to proteins from multiple strains of S. pneumoniae and were against surface-exposed epitopes. Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain. In contrast, immunization with the 20-kDa portion of the PhpA protein did not protect mice. These results suggest that rPhpA-79 is a potential candidate for use as a vaccine against pneumococcal systemic disease and otitis media.
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The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the current conjugate vaccine may still cause pneumococcal disease. To address these serotypes and the remaining otitis media due to Streptococcus pneumoniae , we have been evaluating antigenically conserved proteins from S. pneumoniae as vaccine candidates. A previous report identified a 20-kDa protein with putative human complement C3-proteolytic activity. By utilizing the publicly released pneumococcal genomic sequences, we found the gene encoding the 20-kDa protein to be part of a putative open reading frame of approximately 2,400 bp. We recombinantly expressed a 79-kDa fragment (rPhpA-79) that contains a repeated HxxHxH motif and evaluated it for vaccine potential. The antibodies elicited by the purified rPhpA-79 protein were cross-reactive to proteins from multiple strains of S. pneumoniae and were against surface-exposed epitopes. Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain. In contrast, immunization with the 20-kDa portion of the PhpA protein did not protect mice. These results suggest that rPhpA-79 is a potential candidate for use as a vaccine against pneumococcal systemic disease and otitis media.
Author Ying Zhang
Vicki Barniak
Amy W. Masi
Ken Mountzouros
Margaret K. Hostetter
Bruce A. Green
AuthorAffiliation Departments of Immunology 1 and Bacteriology 2 Research, Wyeth Lederle Vaccines, West Henrietta, New York, and Department of Children's Health, Yale University School of Medicine, New Haven, Connecticut 3
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Issue 6
Keywords Still disease
Middle ear disease
Diseases of the osteoarticular system
Systemic
Histidine
Antigenicity
Streptococcal infection
Systemic disease
Bacteria
Micrococcales
ENT disease
Recombinant protein
Serotype
Anthropogenic factor
Human
Rodentia
Vaccine
Protein A
Streptococcus pneumoniae
Infection
Streptococcaceae
Vertebrata
Mammalia
Mouse
Aminoacid
Bacteriosis
Otitis media
Conjugation
Language English
License CC BY 4.0
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Corresponding author. Mailing address: Wyeth-Lederle Vaccines, 211 Bailey Rd., West Henrietta, NY 14586-9728. Phone: (716) 273-7681. Fax: (716) 273-7515. E-mail: zhangy4@war.wyeth.com.
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Snippet Classifications Services IAI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit...
The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine....
ABSTRACT The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the...
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SubjectTerms Administration, Intranasal
Animals
Antibodies, Bacterial - blood
Bacterial diseases
Bacterial Proteins - genetics
Bacterial Proteins - immunology
Bacteriology
Biological and medical sciences
Endopeptidases - chemistry
Endopeptidases - genetics
Endopeptidases - immunology
Endopeptidases - metabolism
Experimental bacterial diseases and models
Fundamental and applied biological sciences. Psychology
Histidine - chemistry
Humans
Immunization
Infectious diseases
Male
Medical sciences
Mice
Mice, Inbred CBA
Microbial Immunity and Vaccines
Microbiology
Molecular Sequence Data
Nasopharynx - microbiology
Otitis Media - microbiology
Otitis Media - prevention & control
PhpA protein
Pneumococcal Infections - microbiology
Pneumococcal Infections - prevention & control
Pneumococcal Vaccines - immunology
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Recombinant Proteins - metabolism
Sequence Analysis, DNA
Streptococcal Vaccines
Streptococcus pneumoniae
Streptococcus pneumoniae - immunology
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Title Recombinant PhpA Protein, a Unique Histidine Motif-Containing Protein from Streptococcus pneumoniae, Protects Mice against Intranasal Pneumococcal Challenge
URI http://iai.asm.org/content/69/6/3827.abstract
https://www.ncbi.nlm.nih.gov/pubmed/11349048
https://search.proquest.com/docview/17867967
https://search.proquest.com/docview/70849700
https://pubmed.ncbi.nlm.nih.gov/PMC98401
Volume 69
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