Cell-mediated immune proliferative responses to HIV-1 of chimpanzees vaccinated with different vaccinia recombinant viruses.
The only animal that can be reproducibly infected with HIV, and that thus provides an experimental system for testing the effectiveness of prototype vaccines, is the chimpanzee. We compared proliferative responses to HIV and to vaccinia virus (VV) antigens of lymphocytes taken at various times from chimpanzees vaccinated with recombinant VV expressing different HIV genes. Animals were immunized with the original VV strain, as control, or with constructs expressing gp160 (VV160) given exclusively or in combination with one or two other constructs producing p25 (VV25), F/3'-orf (VVF), or the human interleukin-2 (IL-2) gene, which was included in an attempt to amplify immune responses. Irrespective of the HIV gene utilized, lymphocyte proliferation to HIV was usually weak and rapidly decreased after each inoculation, contrasting with strong and sustained responses to VV. Lack of adequate recall reactivity after challenge with fixed autologous lymphocytes expressing VV-produced HIV antigens indicated that vaccination resulted only in low levels of HIV-specific memory cell priming. The use of IL-2-producing VV did not lead to increased responsiveness. Reactivity to soluble purified gp160, but not to p25, could be detected in PBL from animals that had received both VV160 and VV25, while immunization with VVF resulted in a significant response to this protein in one of two animals. The transient nature of T cell reactivity to HIV might explain why, in similar studies, chimpanzees were not protected from infection with live HIV.
Van Eendenburg
J P
JP
UER Pitié-Salpêtrière, Paris, France.
Yagello
M
M
Girard
M
M
Kieny
M P
MP
Lecocq
J P
JP
Muchmore
E
E
Fultz
P N
PN
Riviere
Y
Y
Montagnier
L
L
Gluckman
J C
JC
D000818:Animals; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D000939:Epitopes; D015683:Gene Products, gag; D015693:Gene Products, nef; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D002679:Pan troglodytes / Q000276:immunology*; D012191:Retroviridae Proteins / Q000276:immunology; D014612:Vaccines / Q000494:pharmacology*; D014614:Vaccines, Synthetic / Q000494:pharmacology*; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus
C000715594:CBX5 protein, human; D000939:Epitopes; D015683:Gene Products, gag; D015693:Gene Products, nef; D019302:HIV Envelope Protein gp160; C059827:HIV gag protein p25; D007376:Interleukin-2; D012191:Retroviridae Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D000090266:Chromobox Protein Homolog 5