Effect of the V3 loop deletion of envelope glycoprotein on cellular responses and protection against challenge with recombinant vaccinia virus expressing gp160 of primary human immunodeficiency virus type 1 isolates.
The magnitude and breadth of cytotoxic-T-lymphocyte (CTL) responses induced by human immunodeficiency virus type 1 (HIV-1) envelope protein from which the hypervariable V3 loop had been deleted (DeltaV3) were evaluated in the HLA-A2/K(b) transgenic mice. It was demonstrated that vaccines expressing the DeltaV3 mutant of either HIV-1(IIIB) or HIV-1(89.6) envelope glycoprotein induced broader CD8(+) T-cell activities than those elicited by the wild-type (WT) counterparts. Specifically, the differences were associated with higher responses to conserved HLA-A2-restricted CTL epitopes of the envelope glycoprotein and could be correlated with an increased cell surface occupancy by the epitope-HLA-A2 complexes in target cells expressing the DeltaV3 mutant. Using recombinant vaccinia virus expressing heterologous gp160 of primary HIV-1 isolates in a murine challenge system, we observed that the extent of resistance to viral transmission was higher in animals immunized with the DeltaV3 than the WT envelope vaccine. The protection was linked to the presence of envelope-specific CD8(+) T cells, since depletion of these cells by anti-CD8 antibody treatment at the time of challenge abolished the vaccine-induced protection. The results from our studies provide insights into approaches for boosting the breadth of envelope-specific CTL responses.
Kiszka
Irena
I
Center for Neurovirology and Cancer Biology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Kmieciak
Dariusz
D
Gzyl
Jaroslaw
J
Naito
Toshio
T
Bolesta
Elizabeth
E
Sieron
Aleksander
A
Singh
Satya P
SP
Srinivasan
Alagarsamy
A
Trinchieri
Giorgio
G
Kaneko
Yutaro
Y
Kozbor
Danuta
D
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D017353:Gene Deletion; D006183:H-2 Antigens / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D015789:HLA-A2 Antigen; D010446:Peptide Fragments