A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice.
HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice were created and their immunological potential evaluated in response to hepatitis B DNA vaccine. Every single immunized mouse developed hepatitis B virus-specific antibodies, HLA-DR1-restricted helper, and HLA-A2.1-restricted cytolytic T cell responses directed at the same immunodominant epitopes as those identified in naturally infected or vaccinated humans. These mice were specifically protected against a hepatitis B-recombinant vaccinia virus infection with a 10,000-fold or more reduction of the virus load at day 4 post-challenge. These mice represent a unique in vivo experimental model for human immune function studies without any interference with mouse MHC response which dwarfed the prediction of human responses. Furthermore, they enable the complete monitoring of immune adaptative responses for preclinical screening of candidate vaccines.
Pajot
Anthony
A
Unité d'Immunité Cellulaire Antivirale, Département d'Immunologie, Institut Pasteur, Paris, France.
Michel
Marie-Louise
ML
Fazilleau
Nicolas
N
Pancré
Véronique
V
Auriault
Claude
C
Ojcius
David M
DM
Lemonnier
François A
FA
Lone
Yu-Chun
YC
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D008969:Molecular Sequence Data; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
D000914:Antibodies, Viral; D006183:H-2 Antigens; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA