Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160.
SCID mice reconstituted with adult human peripheral blood leukocytes (hu-PBL-SCID mice) make antigen-specific human antibody responses following secondary immunization and can be infected with human immunodeficiency virus 1 (HIV-1), suggesting that they might prove useful for evaluating protective immunity to HIV-1 following vaccination of PBL donors. HIV-seronegative volunteers were immunized with vaccinia expressing HIV-1LAV-1/Bru 160-kDa envelope glycoprotein (vaccinia gp160) and subsequently given booster injections of recombinant gp160 protein (rgp160). Their PBLs were used at intervals of 4-72 weeks after booster injections to construct hu-PBL-SCID mice, which were then challenged with 10(2)-10(3) minimal animal infectious doses of highly homologous HIV-1IIIB. Control hu-PBL-SCID mice were constructed from donors receiving vaccinia, alum, or hepatitis B vaccine. Protection against virus infection was defined as the absence of HIV-1 by culture and no detection of proviral genomes following PCR amplification. Control animals were highly susceptible to HIV infection. By contrast, hu-PBL-SCID mice reconstituted with cells from three of four donors immunized with vaccinia gp160 and recently injected with rgp160 showed no evidence of HIV-1 infection by culture or PCR assays. With increasing time after rgp160 injection, the ability of vaccine-derived hu-PBL-SCID mice to resist HIV-1 infection diminished. These results demonstrate that a potentially protective human immune response was stimulated by this HIV gp160 immunization protocol and show the utility of the hu-PBL-SCID model in the rapid evaluation of candidate vaccines.
Mosier
D E
DE
Division of Immunology, Medical Biology Institute, La Jolla, CA 92037.
Gulizia
R J
RJ
MacIsaac
P D
PD
Corey
L
L
Greenberg
P D
PD
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D000328:Adult; D000818:Animals; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D016219:Immunotherapy, Adoptive; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009500:Neutralization Tests; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000633:toxicity; D014616:Vaccinia virus / Q000276:immunology*; D014779:Virus Replication
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic