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Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human CD46-transgenic mice: Comparison with a fiber-substituted Ad vector containing fiber proteins of Ad serotype 35.
J Control Release. 2010 Dec 01; 148(2):212-8.JC

Abstract

Recently, much attention has focused on replication-incompetent adenovirus (Ad) vectors containing fiber proteins derived from species B Ad serotype 35 (Ad35) (Ad5F35) and Ad vectors fully constructed from Ad35 as vaccine vectors expressing antigens. However, differences in the transduction properties, including the induction of innate immunity, of Ad5F35 and Ad35 vectors have not been properly and fully examined, partly because the transduction properties of these Ad vectors should be evaluated using nonhuman primates or human CD46-transgenic (CD46TG) mice, which ubiquitously express the primary receptor of Ad35, human CD46, in a pattern similar to that of humans. In the present study, we evaluated innate immune responses of mouse dendritic cells (mDCs) derived from bone marrow cells of wild-type (WT) and CD46TG mice following transduction with Ad serotype 5 (Ad5), fiber-substituted Ad5F35, or Ad35 vectors. Ad5F35 and Ad35 vectors mediated more efficient transduction in mDCs derived from CD46TG mice (CD46TG-mDCs) than did Ad5 vectors. Upregulation of costimulatory molecules and inflammatory cytokine induction by Ad5F35 and Ad35 vectors were significantly higher than those by Ad5 vectors in CD46TG-mDCs. However, the induction properties of the innate immune responses were different between Ad5F35 and Ad35 vectors. Ad35 vectors induced higher levels of costimulatory molecule expression and inflammatory cytokine production than did Ad5F35 vectors in CD46TG-mDCs. Furthermore, intravenous administration of Ad35 vectors in WT and CD46TG mice resulted in higher levels of serum interleukin (IL)-6 and IL-12 compared with administration of Ad5F35 vectors, which exhibited almost mock-transduced levels of these inflammatory cytokines. This study indicates that innate immune responses by Ad35 and Ad5F35 vectors are distinct even although both Ad vectors recognize human CD46 as a receptor.

Authors+Show Affiliations

Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Ibaraki-City, Osaka, Japan. sakurai@nibio.go.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20800630

Citation

Sakurai, Fuminori, et al. "Adenovirus Serotype 35 Vector-induced Innate Immune Responses in Dendritic Cells Derived From Wild-type and Human CD46-transgenic Mice: Comparison With a Fiber-substituted Ad Vector Containing Fiber Proteins of Ad Serotype 35." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 148, no. 2, 2010, pp. 212-8.
Sakurai F, Nakashima K, Yamaguchi T, et al. Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human CD46-transgenic mice: Comparison with a fiber-substituted Ad vector containing fiber proteins of Ad serotype 35. J Control Release. 2010;148(2):212-8.
Sakurai, F., Nakashima, K., Yamaguchi, T., Ichinose, T., Kawabata, K., Hayakawa, T., & Mizuguchi, H. (2010). Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human CD46-transgenic mice: Comparison with a fiber-substituted Ad vector containing fiber proteins of Ad serotype 35. Journal of Controlled Release : Official Journal of the Controlled Release Society, 148(2), 212-8. https://doi.org/10.1016/j.jconrel.2010.08.025
Sakurai F, et al. Adenovirus Serotype 35 Vector-induced Innate Immune Responses in Dendritic Cells Derived From Wild-type and Human CD46-transgenic Mice: Comparison With a Fiber-substituted Ad Vector Containing Fiber Proteins of Ad Serotype 35. J Control Release. 2010 Dec 1;148(2):212-8. PubMed PMID: 20800630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human CD46-transgenic mice: Comparison with a fiber-substituted Ad vector containing fiber proteins of Ad serotype 35. AU - Sakurai,Fuminori, AU - Nakashima,Kazuko, AU - Yamaguchi,Tomoko, AU - Ichinose,Takako, AU - Kawabata,Kenji, AU - Hayakawa,Takao, AU - Mizuguchi,Hiroyuki, Y1 - 2010/08/26/ PY - 2010/05/18/received PY - 2010/07/22/revised PY - 2010/08/19/accepted PY - 2010/8/31/entrez PY - 2010/8/31/pubmed PY - 2011/3/11/medline SP - 212 EP - 8 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 148 IS - 2 N2 - Recently, much attention has focused on replication-incompetent adenovirus (Ad) vectors containing fiber proteins derived from species B Ad serotype 35 (Ad35) (Ad5F35) and Ad vectors fully constructed from Ad35 as vaccine vectors expressing antigens. However, differences in the transduction properties, including the induction of innate immunity, of Ad5F35 and Ad35 vectors have not been properly and fully examined, partly because the transduction properties of these Ad vectors should be evaluated using nonhuman primates or human CD46-transgenic (CD46TG) mice, which ubiquitously express the primary receptor of Ad35, human CD46, in a pattern similar to that of humans. In the present study, we evaluated innate immune responses of mouse dendritic cells (mDCs) derived from bone marrow cells of wild-type (WT) and CD46TG mice following transduction with Ad serotype 5 (Ad5), fiber-substituted Ad5F35, or Ad35 vectors. Ad5F35 and Ad35 vectors mediated more efficient transduction in mDCs derived from CD46TG mice (CD46TG-mDCs) than did Ad5 vectors. Upregulation of costimulatory molecules and inflammatory cytokine induction by Ad5F35 and Ad35 vectors were significantly higher than those by Ad5 vectors in CD46TG-mDCs. However, the induction properties of the innate immune responses were different between Ad5F35 and Ad35 vectors. Ad35 vectors induced higher levels of costimulatory molecule expression and inflammatory cytokine production than did Ad5F35 vectors in CD46TG-mDCs. Furthermore, intravenous administration of Ad35 vectors in WT and CD46TG mice resulted in higher levels of serum interleukin (IL)-6 and IL-12 compared with administration of Ad5F35 vectors, which exhibited almost mock-transduced levels of these inflammatory cytokines. This study indicates that innate immune responses by Ad35 and Ad5F35 vectors are distinct even although both Ad vectors recognize human CD46 as a receptor. SN - 1873-4995 UR - https://www.unboundmedicine.com/medline/citation/20800630/Adenovirus_serotype_35_vector_induced_innate_immune_responses_in_dendritic_cells_derived_from_wild_type_and_human_CD46_transgenic_mice:_Comparison_with_a_fiber_substituted_Ad_vector_containing_fiber_proteins_of_Ad_serotype_35_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(10)00708-X DB - PRIME DP - Unbound Medicine ER -