Tags

Type your tag names separated by a space and hit enter

Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.
Hum Gene Ther. 1997 Jan 01; 8(1):99-109.HG

Abstract

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Authors+Show Affiliations

Division of Pulmonary and Critical Care Medicine, New York Hospital-Cornell Medical Center, New York 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8989999

Citation

Mack, C A., et al. "Circumvention of Anti-adenovirus Neutralizing Immunity By Administration of an Adenoviral Vector of an Alternate Serotype." Human Gene Therapy, vol. 8, no. 1, 1997, pp. 99-109.
Mack CA, Song WR, Carpenter H, et al. Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype. Hum Gene Ther. 1997;8(1):99-109.
Mack, C. A., Song, W. R., Carpenter, H., Wickham, T. J., Kovesdi, I., Harvey, B. G., Magovern, C. J., Isom, O. W., Rosengart, T., Falck-Pedersen, E., Hackett, N. R., Crystal, R. G., & Mastrangeli, A. (1997). Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype. Human Gene Therapy, 8(1), 99-109.
Mack CA, et al. Circumvention of Anti-adenovirus Neutralizing Immunity By Administration of an Adenoviral Vector of an Alternate Serotype. Hum Gene Ther. 1997 Jan 1;8(1):99-109. PubMed PMID: 8989999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype. AU - Mack,C A, AU - Song,W R, AU - Carpenter,H, AU - Wickham,T J, AU - Kovesdi,I, AU - Harvey,B G, AU - Magovern,C J, AU - Isom,O W, AU - Rosengart,T, AU - Falck-Pedersen,E, AU - Hackett,N R, AU - Crystal,R G, AU - Mastrangeli,A, PY - 1997/1/1/pubmed PY - 1997/1/1/medline PY - 1997/1/1/entrez SP - 99 EP - 109 JF - Human gene therapy JO - Hum Gene Ther VL - 8 IS - 1 N2 - Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector. SN - 1043-0342 UR - https://www.unboundmedicine.com/medline/citation/8989999/Circumvention_of_anti_adenovirus_neutralizing_immunity_by_administration_of_an_adenoviral_vector_of_an_alternate_serotype_ L2 - https://www.liebertpub.com/doi/10.1089/hum.1997.8.1-99?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -