Evaluation of human immunodeficiency virus type 1 subtype C gag, pol, and gagpol DNA and alphavirus replicon vaccines.
The worldwide HIV-1 vaccine research endeavor is focused increasingly on subtype C, which is now the predominant strain of the present HIV/AIDS epidemic. Expression cassettes of HIV-1 subtype C gag, pol and versions of gagpol fusion cassettes were constructed and evaluated for their relative abilities to induce cellular immune responses in mice. Animals were vaccinated with DNA or alphavirus replicon particle-based vaccines and cellular immune responses were measured by flow cytometry. Five new major histocompatibility complex (MHC) class I-restricted T cell epitopes in subtype C Gag and Pol were identified. Although two CD8(+) T cell epitopes within Gag were immunodominant in BALB/c and CB6F1 mice, the overall breadth of the T cell responses in mice immunized with plasmids or recombinant alphavirus replicon particles encoding gagpol fusion genes was improved over single antigen genes (i.e. gag or pol alone). The patterns of epitope dominance were consistent among mice although there were variations observed between different animals in the relative contributions of the various epitopes to the total response. These data are consistent with observations in non-human primates (Otten GR, Schaefer M, Doe B, Liu H, Magede JZ, Donnelly J, et al. Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in vivo electroporation. Vaccine 2005, in press) and support a subtype C in-frame gagpol fusion gene vaccine.
Megede
Jan Zur
JZ
Vaccines Research, Chiron Corporation, 4560 Horton St., Emeryville, CA 94608, USA. jan_zur_Megede@chiron.com
Otten
Gillis R
GR
Doe
Barbara
B
Liu
Hong
H
Srivastava
Ranjana
R
Greer
Catherine
C
Legg
Harold
H
Tang
Tony
T
Polo
John M
JM
Donnelly
John J
JJ
Ulmer
Jeffrey B
JB
Barnett
Susan W
SW
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000524:Alphavirus / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005260:Female; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000235:genetics* / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics* / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012093:Replicon; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic