Mapping of Epitopes on the Fiber Knobs of Human Adenovirus Serotypes 8 and 15

Abstract

In order to obtain information on the linear antigenic epitopes on fiber knobs of adenovirus serotypes 8 (Ad8) and 15 (Ad15) of subgenus D, the binding of polyclonal virus- and fiber-specific rabbit antibodies to overlapping peptides covering the fiber knob was studied. The main antigenic epitopes of the fiber knob of Ad8 (FK8) were represented by the peptides P4 [amino acids (aa) 213–227], P6 (aa 233–247), P11 (aa 283–297), P13 (aa 303–317) and P15 (aa 316–325); the peptides P1 (aa 183–197), P8 (aa 253–267), P10 (aa 273–287) and P23 (aa 340–349) were moderately reactive. The peptides P4, P6, P11, P13 and P15 span the β strands C, D, G and H, parts of the CD and DG loops and the complete GH loop of the fiber knob. The main epitopes of the fiber knob of Ad15 (FK15) were represented by peptides P5 (aa 198–212), P10 (aa 223–237), P12 (aa 233–247), P13 (aa 238–252), P26 (aa 303–317), P29 (aa 318–332) and P32 (aa 333–347), spanning the β strands B, D, G, H and I, partly strand C, the CD loop, parts of the AB and DG loops, the GH and HI loops and the N-terminal part of the IJ loop. The amino acid sequence alignment showed that the location of the linear FK8 and FK15 epitopes was found to be overlapping to a major extent. Two serotype-specific epitopes were determined on FK15, represented by P10 and P13.

Identification of Adenovirus (Ad) Penton Base Neutralizing Epitopes by Use of Sera from Patients Who Had Received Conditionally Replicative Ad (Ad dl 1520) for Treatment of Liver Tumors

“…3) Phage-mediated depletion of RGD-and other epitope-directed Pb antibodies. In order to determine the contribution of anti-RGD antibody in Ad vector NA, the unique phage carrying the epitope RGDVTF was amplified and incubated with 17 different serum samples which had Pb antibodies and moderate to high Ad NA titers (D10 samples from patients 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, and 16 and samples 18,19,20, and 21 from healthy donors). After removal of the phage (RGD)-antibody complexes by centrifugation, the serum supernatants were tested for Ad NA, which were indirectly assayed by their effect on gene transduction by using the Ad5Luc3 vector.…”

“…The sera of the patients before and after Ad administration were analyzed for their NA effect on Ad infection, and their reactivity against the three major Ad capsid proteins: hexon, fiber, and Pb. Several research groups have shown Ad capsid epitopes in hexon (5,32) and fiber (6,(19)(20)(21) proteins that were responsible for the immune response. However, the immunogenicity in humans and the characterization of neutralizing and nonneutralizing epitopes in the third major Ad capsid component, the Pb, has not been systematically studied.…”

CAR chasing: canine adenovirus vectors–all bite and no bark?

“…This is not so surprising. Analysis of the regions that are highly conserved among human adenovirus serotypes [78][79][80]107] suggests that CAV-2 shares some conserved antigenic epitopes. The question is how many different antigens need to be present before it becomes problematic in the clinic.…”

Localization of neutralization epitopes on adenovirus fiber knob from species C

“…Many previous studies have mapped linear epitopes on the fiber knobs of Ad2, Ad3, Ad5, Ad8 and Ad15, and several type-specific antigenic epitopes on the knob can be identified by ELISA and other methods (Fender et al, 1995;Liebermann et al, 1998Liebermann et al, , 2001Liebermann et al, , 2002. However, few studies have been carried out to identify the neutralization epitopes on the AdV fiber knob.…”