Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF

Stefan Worgall, Anja Krause, JianPing Qiu, Ju Joh, Neil R. Hackett, Ronald Crystal

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1- E3 - adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

Original languageEnglish
Pages (from-to)13801-13808
Number of pages8
JournalJournal of Virology
Volume81
Issue number24
DOIs
Publication statusPublished - 1 Dec 2007
Externally publishedYes

Fingerprint

Capsid
Adenoviridae
Pseudomonas aeruginosa
Immunity
Immunization
Pseudomonas Vaccines
Genes
Antigen-Presenting Cells
Inbred C57BL Mouse
Integrins
Dendritic Cells
Interferon-gamma
Agar
Epitopes
Anti-Idiotypic Antibodies
Vaccines
Genome
T-Lymphocytes
Lung
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF. / Worgall, Stefan; Krause, Anja; Qiu, JianPing; Joh, Ju; Hackett, Neil R.; Crystal, Ronald.

In: Journal of Virology, Vol. 81, No. 24, 01.12.2007, p. 13801-13808.

Research output: Contribution to journalArticle

Worgall, Stefan ; Krause, Anja ; Qiu, JianPing ; Joh, Ju ; Hackett, Neil R. ; Crystal, Ronald. / Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF. In: Journal of Virology. 2007 ; Vol. 81, No. 24. pp. 13801-13808.
@article{422dd1be84ba4a5780b87f7f4fcc0d2f,
title = "Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF",
abstract = "This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1- E3 - adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.",
author = "Stefan Worgall and Anja Krause and JianPing Qiu and Ju Joh and Hackett, {Neil R.} and Ronald Crystal",
year = "2007",
month = "12",
day = "1",
doi = "10.1128/JVI.01246-07",
language = "English",
volume = "81",
pages = "13801--13808",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "24",

}

TY - JOUR

T1 - Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF

AU - Worgall, Stefan

AU - Krause, Anja

AU - Qiu, JianPing

AU - Joh, Ju

AU - Hackett, Neil R.

AU - Crystal, Ronald

PY - 2007/12/1

Y1 - 2007/12/1

N2 - This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1- E3 - adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

AB - This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1- E3 - adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

UR - http://www.scopus.com/inward/record.url?scp=37049036174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37049036174&partnerID=8YFLogxK

U2 - 10.1128/JVI.01246-07

DO - 10.1128/JVI.01246-07

M3 - Article

VL - 81

SP - 13801

EP - 13808

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 24

ER -