Characterization of gene use and efficacy of mouse monoclonal antibodies to Streptococcus pneumoniae serotype 8

Masahide Yano, Liise-anne Pirofski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V H) and light (VL) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and VH gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalClinical and Vaccine Immunology
Volume18
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Streptococcus pneumoniae
Phosphorylcholine
Genes
Polysaccharides
Monoclonal Antibodies
Pneumococcal Vaccines
Vaccines
Pneumonia
Conjugate Vaccines
Tetanus Toxoid
Antibodies
Molecular Structure
Germ Cells
Molecular structure
Uncertainty
Antibody Formation
Serogroup
Epitopes
Nucleotides
Availability

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Characterization of gene use and efficacy of mouse monoclonal antibodies to Streptococcus pneumoniae serotype 8. / Yano, Masahide; Pirofski, Liise-anne.

In: Clinical and Vaccine Immunology, Vol. 18, No. 1, 01.2011, p. 59-66.

Research output: Contribution to journalArticle

@article{874b138d689443f49049c7c84e2b58b2,
title = "Characterization of gene use and efficacy of mouse monoclonal antibodies to Streptococcus pneumoniae serotype 8",
abstract = "Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V H) and light (VL) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and VH gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.",
author = "Masahide Yano and Liise-anne Pirofski",
year = "2011",
month = "1",
doi = "10.1128/CVI.00368-10",
language = "English (US)",
volume = "18",
pages = "59--66",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Characterization of gene use and efficacy of mouse monoclonal antibodies to Streptococcus pneumoniae serotype 8

AU - Yano, Masahide

AU - Pirofski, Liise-anne

PY - 2011/1

Y1 - 2011/1

N2 - Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V H) and light (VL) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and VH gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.

AB - Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V H) and light (VL) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and VH gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.

UR - http://www.scopus.com/inward/record.url?scp=78650905191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650905191&partnerID=8YFLogxK

U2 - 10.1128/CVI.00368-10

DO - 10.1128/CVI.00368-10

M3 - Article

C2 - 21068211

AN - SCOPUS:78650905191

VL - 18

SP - 59

EP - 66

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 1

ER -