Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector specific immune response

G. Sailaja, Harm HogenEsch, A. North, J. Hays, S. K. Mittal

Research output: Contribution to journalReview article

80 Citations (Scopus)

Abstract

Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and naïve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial β-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1 x) or twice (2 x) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated naïve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P > 0. 05) in LacZ expression in mice immunized 1 x or 2 x with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated naïve animals. Similar results were obtained with i. n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.

Original languageEnglish (US)
Pages (from-to)1722-1729
Number of pages8
JournalGene Therapy
Volume9
Issue number24
DOIs
StatePublished - Dec 2002
Externally publishedYes

Fingerprint

Human Adenoviruses
Microspheres
Adenoviridae
Galactosidases
Viruses
Drug Compounding
Lac Operon
Genetic Therapy
Immunity
Suspensions
Vaccination
alginic acid
Antibodies

Keywords

  • Adenovirus encapsulation
  • Adenovirus recombinant
  • Alginate microspheres
  • Delivery vehicle
  • Vector-specific immune response

ASJC Scopus subject areas

  • Genetics

Cite this

Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector specific immune response. / Sailaja, G.; HogenEsch, Harm; North, A.; Hays, J.; Mittal, S. K.

In: Gene Therapy, Vol. 9, No. 24, 12.2002, p. 1722-1729.

Research output: Contribution to journalReview article

Sailaja, G. ; HogenEsch, Harm ; North, A. ; Hays, J. ; Mittal, S. K. / Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector specific immune response. In: Gene Therapy. 2002 ; Vol. 9, No. 24. pp. 1722-1729.
@article{033122a9788a4ece9f2cf8a332d1412a,
title = "Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector specific immune response",
abstract = "Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and na{\"i}ve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial β-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1 x) or twice (2 x) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated na{\"i}ve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P > 0. 05) in LacZ expression in mice immunized 1 x or 2 x with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated na{\"i}ve animals. Similar results were obtained with i. n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.",
keywords = "Adenovirus encapsulation, Adenovirus recombinant, Alginate microspheres, Delivery vehicle, Vector-specific immune response",
author = "G. Sailaja and Harm HogenEsch and A. North and J. Hays and Mittal, {S. K.}",
year = "2002",
month = "12",
doi = "10.1038/sj.gt.3301858",
language = "English (US)",
volume = "9",
pages = "1722--1729",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "24",

}

TY - JOUR

T1 - Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector specific immune response

AU - Sailaja, G.

AU - HogenEsch, Harm

AU - North, A.

AU - Hays, J.

AU - Mittal, S. K.

PY - 2002/12

Y1 - 2002/12

N2 - Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and naïve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial β-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1 x) or twice (2 x) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated naïve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P > 0. 05) in LacZ expression in mice immunized 1 x or 2 x with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated naïve animals. Similar results were obtained with i. n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.

AB - Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and naïve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial β-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1 x) or twice (2 x) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated naïve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P > 0. 05) in LacZ expression in mice immunized 1 x or 2 x with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated naïve animals. Similar results were obtained with i. n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.

KW - Adenovirus encapsulation

KW - Adenovirus recombinant

KW - Alginate microspheres

KW - Delivery vehicle

KW - Vector-specific immune response

UR - http://www.scopus.com/inward/record.url?scp=0036956812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036956812&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3301858

DO - 10.1038/sj.gt.3301858

M3 - Review article

VL - 9

SP - 1722

EP - 1729

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 24

ER -