Novel replication-incompetent vector derived from adenovirus type 11 (Ad11) for vaccination and gene therapy: low seroprevalence and non-cross-reactivity with Ad5.
A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent (DeltaE1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV(+)) individuals is as low as that among HIV(-) individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and dendritic cells and cardiovascular tissues with higher efficiency than Ad5. Ad11 and Ad35 appear to have a similar tropism as judged by green fluorescent protein expression levels determined by using a panel of cancer cell lines. In addition, Ad5 preimmunization did not significantly affect Ad11-mediated transduction in C57BL/6 mice. We therefore conclude that the Ad11-based vector represents a novel and useful candidate gene transfer vehicle for vaccination and gene therapy.
Holterman
Lennart
L
Crucell Holland BV, Leiden, The Netherlands.
Vogels
Ronald
R
van der Vlugt
Remko
R
Sieuwerts
Martijn
M
Grimbergen
Jos
J
Kaspers
Jorn
J
Geelen
Eric
E
van der Helm
Esmeralda
E
Lemckert
Angelique
A
Gillissen
Gert
G
Verhaagh
Sandra
S
Custers
Jerome
J
Zuijdgeest
David
D
Berkhout
Ben
B
Bakker
Margreet
M
Quax
Paul
P
Goudsmit
Jaap
J
Havenga
Menzo
M
D000260:Adenoviruses, Human / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D003429:Cross Reactions; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D018523:Tropism; D014611:Vaccination; D014779:Virus Replication
D000914:Antibodies, Viral; D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins