Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF

Anja Krause, Wen Zhu Whu, Yaqin Xu, Ju Joh, Ronald Crystal, Stefan Worgall

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p> 0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p> 0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p< 0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.

Original languageEnglish
Pages (from-to)2131-2139
Number of pages9
JournalVaccine
Volume29
Issue number11
DOIs
Publication statusPublished - 31 Jan 2011
Externally publishedYes

Fingerprint

mucosal immunity
Mucosal Immunity
Pseudomonas aeruginosa
Cellular Immunity
cell-mediated immunity
lungs
Lung
Immunization
immunization
proteins
Vaccines
T-lymphocytes
dendritic cells
T-Lymphocytes
Dendritic Cells
Immunity
serotypes
Immunoglobulin G
immunity
Pseudomonas aeruginosa OprF protein

Keywords

  • Mucosal immunity
  • Pseudomonas
  • Viral vectors

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF. / Krause, Anja; Whu, Wen Zhu; Xu, Yaqin; Joh, Ju; Crystal, Ronald; Worgall, Stefan.

In: Vaccine, Vol. 29, No. 11, 31.01.2011, p. 2131-2139.

Research output: Contribution to journalArticle

Krause, Anja ; Whu, Wen Zhu ; Xu, Yaqin ; Joh, Ju ; Crystal, Ronald ; Worgall, Stefan. / Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF. In: Vaccine. 2011 ; Vol. 29, No. 11. pp. 2131-2139.
@article{2d184eb932bb4232839e4ffeae88f310,
title = "Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF",
abstract = "Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p> 0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p> 0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p< 0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.",
keywords = "Mucosal immunity, Pseudomonas, Viral vectors",
author = "Anja Krause and Whu, {Wen Zhu} and Yaqin Xu and Ju Joh and Ronald Crystal and Stefan Worgall",
year = "2011",
month = "1",
day = "31",
doi = "10.1016/j.vaccine.2010.12.087",
language = "English",
volume = "29",
pages = "2131--2139",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "11",

}

TY - JOUR

T1 - Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF

AU - Krause, Anja

AU - Whu, Wen Zhu

AU - Xu, Yaqin

AU - Joh, Ju

AU - Crystal, Ronald

AU - Worgall, Stefan

PY - 2011/1/31

Y1 - 2011/1/31

N2 - Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p> 0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p> 0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p< 0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.

AB - Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p> 0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p> 0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p< 0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.

KW - Mucosal immunity

KW - Pseudomonas

KW - Viral vectors

UR - http://www.scopus.com/inward/record.url?scp=79951811903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951811903&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2010.12.087

DO - 10.1016/j.vaccine.2010.12.087

M3 - Article

VL - 29

SP - 2131

EP - 2139

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 11

ER -