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Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160

Academic Article
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Overview

authors

  • Mosier, Donald
  • Gulizia, R. J.
  • Macisaac, P. D.
  • Corey, L.
  • Greenberg, P. D.

publication date

  • 1993

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • 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.

subject areas

  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Adult
  • Animals
  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Gene Products, env
  • HIV Antibodies
  • HIV Envelope Protein gp160
  • HIV-1
  • Humans
  • Immunization Schedule
  • Immunization, Secondary
  • Immunotherapy, Adoptive
  • Leukocyte Transfusion
  • Leukocytes
  • Lymphocyte Activation
  • Mice
  • Mice, SCID
  • Neutralization Tests
  • Protein Precursors
  • Recombinant Proteins
  • T-Lymphocytes
  • Vaccines, Synthetic
  • Vaccinia virus
  • Virus Replication
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Research

keywords

  • ANIMAL MODEL
  • HUMAN IMMUNODEFICIENCY VIRUS-1 VACCINATION
  • IMMUNE RESPONSE
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Identity

PubMed Central ID

  • PMC46103

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.90.6.2443

PubMed ID

  • 8460155
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Additional Document Info

start page

  • 2443

end page

  • 2447

volume

  • 90

issue

  • 6

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