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PMID: 20600496 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28.

Vaccine ·Vol. 28 ·No. 35 ·2010-08-09 ·Pages 5691-702

Kahl CA, Bonnell J, Hiriyanna S, Fultz M, Nyberg-Hoffman C, Chen P, King CR, Gall JG

Abstract

Adenovirus vaccine vectors derived from rare human serotypes have been shown to be less potent than serotype 5 (Ad5) at inducing immune responses to encoded antigens. To identify highly immunogenic adenovirus vectors, we assessed pro-inflammatory cytokine expression, binding to the CD46 receptor, and immunogenicity. Species D adenoviruses uniquely suppressed pro-inflammatory cytokines and induced high levels of type I interferon. Thus, it was unexpected that a vector derived from a representative serotype, Ad28, induced significantly higher transgene-specific T cell responses than an Ad35 vector. Prime-boost regimens with Ad28, Ad35, Ad14, or Ad5 significantly boosted T cell and antibody responses. The seroprevalence of Ad28 was confirmed to be <10% in the United States. Together, this shows that a rare human serotype-based vector can elicit strong immune responses, which was not predicted by in vitro results.

MeSH Terms
Adenoviruses, Human/immunology Adolescent Adult Aged Animals Antibody Formation CD8-Positive T-Lymphocytes/immunology Cell Line Cytokines/immunology Female Genetic Vectors Humans Immunity, Cellular Leukocytes, Mononuclear/immunology Male Membrane Cofactor Protein/immunology Mice Mice, Inbred BALB C Middle Aged Neutralization Tests Seroepidemiologic Studies United States Viral Vaccines/immunology Young Adult
Chemicals
Cytokines Membrane Cofactor Protein Viral Vaccines
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kahl Christoph A
GenVec, Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20878, USA.
Bonnell Jessica
Hiriyanna Suja
Fultz Megan
Nyberg-Hoffman Cassandra
Chen Ping
King C Richter
Gall Jason G D
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Article Info
Journal
Vaccine
Abbr.
Vaccine
ISSN
1873-2518
DOI
10.1016/j.vaccine.2010.06.050
Published
2010-08-09
Epub
2010-00-29
Pages
5691-702
Language
English
Region
Netherlands
NLM ID
8406899
PMCID
PMC2927224
Subset
IM
Grants
NIAID NIH HHS · R43 AI062176 · United States
NIAID NIH HHS · R43 AI062176-01A2 · United States
NIAID NIH HHS · R43 AI062176-01A1 · United States
External Links
PubMed source DOI: 10.1016/j.vaccine.2010.06.050 PMC Full Text View journal details
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