Effects of shielding adenoviral vectors with polyethylene glycol on vector-specific and vaccine-mediated immune responses

Eric A. Weaver, Michael A Barry

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the intramuscular or intranasal route. In contrast, PEGylated vectors generally appear better at boosting antibody responses in Ad-immune animals. Displaying either glucose or galactose on PEG mediated increased transduction and antibody responses by the intranasal, but not the intramuscular, route. In naive animals, PEGylated vectors generated T cell responses that were equal to or better than those by unmodified Ad. Priming by PEGylated vectors generally enabled better subsequent T cell responses after boost. Priming and boosting by PEGylated vectors produced T cell responses after boost that were equal to or higher than those produced by unmodified vectors. These data indicate that PEGylation can enable more effective application of Ad5 and perhaps other Ad serotype vaccines during prime-boost vaccination.

Original languageEnglish (US)
Pages (from-to)1369-1382
Number of pages14
JournalHuman Gene Therapy
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2008

Fingerprint

Vaccines
Adenoviridae
Antibody Formation
T-Lymphocytes
Vaccination
Human Adenoviruses
Transgenes
Galactose
Genetic Therapy
Serogroup
Immunity
Polymers
Antigens
Glucose
Genes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Effects of shielding adenoviral vectors with polyethylene glycol on vector-specific and vaccine-mediated immune responses. / Weaver, Eric A.; Barry, Michael A.

In: Human Gene Therapy, Vol. 19, No. 12, 01.12.2008, p. 1369-1382.

Research output: Contribution to journalArticle

@article{e1fa1f6fd1f54ef9b8a3f717177cf01e,
title = "Effects of shielding adenoviral vectors with polyethylene glycol on vector-specific and vaccine-mediated immune responses",
abstract = "Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the intramuscular or intranasal route. In contrast, PEGylated vectors generally appear better at boosting antibody responses in Ad-immune animals. Displaying either glucose or galactose on PEG mediated increased transduction and antibody responses by the intranasal, but not the intramuscular, route. In naive animals, PEGylated vectors generated T cell responses that were equal to or better than those by unmodified Ad. Priming by PEGylated vectors generally enabled better subsequent T cell responses after boost. Priming and boosting by PEGylated vectors produced T cell responses after boost that were equal to or higher than those produced by unmodified vectors. These data indicate that PEGylation can enable more effective application of Ad5 and perhaps other Ad serotype vaccines during prime-boost vaccination.",
author = "Weaver, {Eric A.} and Barry, {Michael A}",
year = "2008",
month = "12",
day = "1",
doi = "10.1089/hum.2008.091",
language = "English (US)",
volume = "19",
pages = "1369--1382",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "12",

}

TY - JOUR

T1 - Effects of shielding adenoviral vectors with polyethylene glycol on vector-specific and vaccine-mediated immune responses

AU - Weaver, Eric A.

AU - Barry, Michael A

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the intramuscular or intranasal route. In contrast, PEGylated vectors generally appear better at boosting antibody responses in Ad-immune animals. Displaying either glucose or galactose on PEG mediated increased transduction and antibody responses by the intranasal, but not the intramuscular, route. In naive animals, PEGylated vectors generated T cell responses that were equal to or better than those by unmodified Ad. Priming by PEGylated vectors generally enabled better subsequent T cell responses after boost. Priming and boosting by PEGylated vectors produced T cell responses after boost that were equal to or higher than those produced by unmodified vectors. These data indicate that PEGylation can enable more effective application of Ad5 and perhaps other Ad serotype vaccines during prime-boost vaccination.

AB - Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the intramuscular or intranasal route. In contrast, PEGylated vectors generally appear better at boosting antibody responses in Ad-immune animals. Displaying either glucose or galactose on PEG mediated increased transduction and antibody responses by the intranasal, but not the intramuscular, route. In naive animals, PEGylated vectors generated T cell responses that were equal to or better than those by unmodified Ad. Priming by PEGylated vectors generally enabled better subsequent T cell responses after boost. Priming and boosting by PEGylated vectors produced T cell responses after boost that were equal to or higher than those produced by unmodified vectors. These data indicate that PEGylation can enable more effective application of Ad5 and perhaps other Ad serotype vaccines during prime-boost vaccination.

UR - http://www.scopus.com/inward/record.url?scp=57749193282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57749193282&partnerID=8YFLogxK

U2 - 10.1089/hum.2008.091

DO - 10.1089/hum.2008.091

M3 - Article

C2 - 18778197

AN - SCOPUS:57749193282

VL - 19

SP - 1369

EP - 1382

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 12

ER -