Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28.
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.
Kahl
Christoph A
CA
GenVec, Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20878, USA.
Bonnell
Jessica
J
Hiriyanna
Suja
S
Fultz
Megan
M
Nyberg-Hoffman
Cassandra
C
Chen
Ping
P
King
C Richter
CR
Gall
Jason G D
JG
D000260:Adenoviruses, Human / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051916:Membrane Cofactor Protein / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009500:Neutralization Tests; D016036:Seroepidemiologic Studies; D014481:United States; D014765:Viral Vaccines / Q000276:immunology*; D055815:Young Adult
D016207:Cytokines; D051916:Membrane Cofactor Protein; D014765:Viral Vaccines