Using HLA-A2.1 transgenic rabbit model to screen and characterize new HLA-A2.1 restricted epitope DNA vaccines

Jiafen Hu, Todd D. Schell, Xuwen Peng, Nancy M. Cladel, Karla K. Balogh, Neil D. Christensen

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5 Citations (Scopus)

Abstract

We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing fi ve HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specifi c protective and therapeutic immunity. Among these fi ve epitopes, two (161- 169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.

Original languageEnglish (US)
JournalJournal of Vaccines and Vaccination
Volume1
Issue number1
DOIs
StatePublished - Oct 1 2010

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DNA Vaccines
Epitopes
Rabbits
Transgenic Mice
Cottontail rabbit papillomavirus
Immunity
Immunization
Animal Models
Peptides
Genetically Modified Animals
Papillomavirus Infections
DNA
Therapeutic Uses
T-Lymphocytes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Drug Discovery
  • Virology

Cite this

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title = "Using HLA-A2.1 transgenic rabbit model to screen and characterize new HLA-A2.1 restricted epitope DNA vaccines",
abstract = "We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing fi ve HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specifi c protective and therapeutic immunity. Among these fi ve epitopes, two (161- 169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.",
author = "Jiafen Hu and Schell, {Todd D.} and Xuwen Peng and Cladel, {Nancy M.} and Balogh, {Karla K.} and Christensen, {Neil D.}",
year = "2010",
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T1 - Using HLA-A2.1 transgenic rabbit model to screen and characterize new HLA-A2.1 restricted epitope DNA vaccines

AU - Hu, Jiafen

AU - Schell, Todd D.

AU - Peng, Xuwen

AU - Cladel, Nancy M.

AU - Balogh, Karla K.

AU - Christensen, Neil D.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing fi ve HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specifi c protective and therapeutic immunity. Among these fi ve epitopes, two (161- 169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.

AB - We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing fi ve HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specifi c protective and therapeutic immunity. Among these fi ve epitopes, two (161- 169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identifi ed the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specifi c CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the fi ve epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specifi c therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.

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