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. 2002 Jul;76(13):6453-9.
doi: 10.1128/jvi.76.13.6453-6459.2002.

Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit papillomavirus induces protective immunity against virus challenge in rabbits

Jiafen Hu  1 , Ricai Han, Nancy M Cladel, Martin D Pickel, Neil D Christensen
Affiliations

Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit papillomavirus induces protective immunity against virus challenge in rabbits

Jiafen Hu et al. J Virol. 2002 Jul.

Abstract

The cottontail rabbit papillomavirus (CRPV)-rabbit model has been used in several studies for testing prophylactic and therapeutic papillomavirus vaccines. Earlier observations had shown that the CRPV nonstructural genes E1, E2, and E6 induced strong to partial protective immunity against CRPV infection. In this study, we found that CRPV E8 immunization eliminated virus-induced papillomas in EIII/JC inbred rabbits (100%) and provided partial protection (55%) against virus challenge in outbred New Zealand White rabbits. CRPV-E8 is a small open reading frame, coding for a 50-amino-acid protein, that is colinear with the CRPV E6 gene and has features similar to those of the bovine papillomavirus and human papillomavirus E5 genes. Papillomas that grew on E8-vaccinated outbred rabbits were significantly smaller than those on vector-vaccinated rabbits (P < 0.01; t test). Delayed-type hypersensitivity skin tests showed that some of the E8-vaccinated rabbits had positive responses to E8-specific peptides.

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Figures

FIG. 1.
FIG. 1.
Mean (± SEM) of papilloma size of E8 knockout and wild-type CRPV DNA (10 μg of DNA per site) on NZW and EIII/JC outbred and inbred rabbits. Groups of five inbred and outbred rabbits were challenged with E8 knockout CRPV, while a second set of five rabbits was challenged with wt CRPV which included the introduced SacII site (see Materials and Methods). Mean papilloma sizes were significantly different (P < 0.001; t test) when E8 knockout CRPV- and wt CRPV-inoculated sites were compared after week 5. N, number of papillomas for each group.
FIG. 2.
FIG. 2.
Mean (± SEM) of papilloma size on outbred and inbred rabbits following genetic vaccinations with vector alone or E8 expression vector. All rabbits were challenged with CRPV (10−2 dilution of stock virus) at four sites on the back of each rabbit. Mean papilloma sizes were significantly different (P < 0.05; t test) when vector and E8 vaccinations for outbred and inbred rabbits were compared. N, number of papillomas for each group.
FIG. 3.
FIG. 3.
DTH skin test reactions to peptide 3 (YCLVLWIFIVTLLLL) on various EIII/JC inbred rabbits (A) and NZW outbred rabbits (B). (A) One of three E8-immunized EIII/JC inbred rabbits (R4 to R6) showed positive skin swelling 96 and 120 h after peptide injection; no swelling was observed on vector-immunized rabbits (R1 to R3) or naïve rabbits (N1 and N2). (B) Two of five E8-immunized NZW outbred rabbits (R6 to R10) showed positive skin swelling 96 h after peptide injection; none of the vector-immunized (R1 to R5) or naïve (N3 and N4) rabbits showed swelling at this time point.
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