Protective cell-mediated immunity by DNA vaccination against papillomavirus L1 capsid protein in the cottontail rabbit papillomavirus model

Papillomavirus major capsid protein L1 has successfully stimulated protective immunity against virus infection by induction of neutralizing antibodies in animal models and in clinical trials. However, the potential impact of L1-induced protective cell-mediated immune (CMI) responses is difficult to measure in vivo because of the coincidence of anti-L1 antibody. In this study, we tested the hypothesis that L could activate CMI, using the Cottontail Rabbit Papillomavirus (CRPV)-rabbit model. A unique property of this model is that infections can be initiated with viral DNA, thus bypassing all contributions to protection via neutralizing anti-L1 antibody. DNA vaccines containing either CRPV L1, or subfragments of L1 (amino-terminal two-thirds of L1 [L1N] and the carboxyl-terminal two-thirds of L1 [L1C]), were delivered intracutaneously into rabbits, using a gene gun. After three booster immunizations, the rabbits were challenged with several viral DNA constructs: wild-type CRPV, CRPV L1ATGko (an L1 ATG knockout mutation), and CRPV-ROPV hybrid (CMPV with a replacement L1 from Rabbit Oral Papillomavirus). Challenge of L1 DNA-vaccinated rabbits with wild-type CRPV resulted in significantly fewer papillomas when compared with challenge with CRPV L1ATGko DNA. Significantly smaller papillomas were found in CRPV L1-, L1N-, and L1C-vaccinated rabbits. In addition, rabbits vaccinated with either L1 or L1N grew significantly fewer and smaller papillomas when challenged with CRPV-ROPV hybrid DNA. Therefore, CRPV L1 DNA vaccination induced CMI responses to CRPV DNA infections that can contribute to protective immunity. Cross-protective immunity against CRPV L1 and ROPV L1 was elicited in these CRPV L1- and subfragment-vaccinated rabbits.

Final publication is available from Mary Ann Liebert, Inc., publishers https://dx.doi.org/10.1089/vim.2006.19.492

Files

Metadata

Work Title Protective cell-mediated immunity by DNA vaccination against papillomavirus L1 capsid protein in the cottontail rabbit papillomavirus model
Access
Open Access
Creators
  1. Jiafen Hu
  2. Nancy M. Cladel
  3. Lynn R. Budgeon
  4. Cynthia A. Reed
  5. Martin D. Pickel
  6. Neil Christensen
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Viral Immunology
Publication Date September 20, 2006
Publisher Identifier (DOI)
  1. https://doi.org/10.1089/vim.2006.19.492
Deposited January 30, 2023

Versions

Analytics

Collections

This resource is currently not in any collection.

Work History

Version 1
published

  • Created
  • Added VI_2006_L1_paper_revision_final.pdf
  • Added Creator Jiafen Hu
  • Added Creator Nancy M. Cladel
  • Added Creator Lynn R. Budgeon
  • Added Creator Cynthia A. Reed
  • Added Creator Martin D. Pickel
  • Added Creator Neil Christensen
  • Published
  • Updated Publication Date Show Changes
    Publication Date
    • 2006-01-01
    • 2006-09-20
  • Added L1 vaccination Figures final.doc
  • Added Tables.doc
  • Updated