Passive immune globulin therapy in the SIV/macaque model: Early interventisn can alter disease profile

Nancy Haigwood, Andrew Watson, William F. Sutton, Jan McClure, Anne Lewis, Jane Ranchalis, Bruce Travis, Gerald Voss, Norman L. Letvin, Shiu Lok Hu, Vanessa M. Hirsch, Philip R. Johnson

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

One of the major questions in AIDS is the role that the host immune system and the virus play in the dynamics of infection and the development of AIDS in an infected individual. In order to test the role of antibody in controlling viral infection, high-dose SIV-immune globulin was passively transferred to infected macaques early in infection. Immune globulin purified from the plasma of an SIV-infected long-term non-progressor macaque (SIVIG) or a pool of normal immune globulin (normal Ig) was infused into STVsmE660-infected macaques (170 mg/kg) at one and fourteen days post infection. Animals were monitored for SIV-specific antibodies, viremia, plasma antigenemia, and clinical course. All animals were infected by SIV. At 16 months post infection, five macaques in the combined control groups have been euthanized, one as a rapid progressor with debilitating disease at 20 weeks post infection. Four macaques from the comparison groups have signs of AIDS, accompanied by high and increasing levels of virus and p27 antigenemia. One of the ten control animals had a very low virus load in plasma and peripheral blood and lymph node mononuclear cells at all times tested and has remained disease-free. In the SIVIG treatment group, two macaques were euthanized at 18-20 weeks due to AIDS, rapid progressors to disease. Three macaques in the SIVIG group had an initial high level of virus in plasma, peripheral blood mononuclear cells (PBMC), and lymph node mononuclear cells (LNMC), which dropped to baseline at 6 weeks post infection and has remained very low or negative for 16 months, a disease profile which has not been observed in untreated animals in this model to date. These macaques have remained clinically healthy. The sixth treated animal is also healthy, with very low virus burden that is detectable only by nested set polymerase chain reaction (PCR). All SIVIG-treated macaques had no detectable p27 plasma antigenemia for the first 10 weeks of infection, demonstrating that the IgG effectively complexed with the virus. The immunological correlates in the treated animals include development of de novo virus-specific antibodies and/or cytotoxic T cell (CTL), both of which are hallmarks of long term non-progressors. The two SIVIG-treated macaques that progress to disease rapidly had no detectable de novo humoral immune responses, as is often seen in rapid HIV disease in humans. Envelope-specific and virus neutralizing antibodies alone were not sufficient to prevent disease progression, as the plasma of both non-progressors as well as progressors had high titers of envelope-specific and neutralizing antibodies against SIVsmE660. Poor clinical prognosis was associated with moderate to high and increasing virus loads in plasma, PBMC, and lymph nodes. Good clinical prognosis correlated with low or undetectable post acute viremia in the peripheral blood and lymph nodes. We hypothesize that SIVIG reduced the spread of virus by eliminating or reducing plasma virus through immune complexes during the first four to 8 weeks of infection and then maintaining this low level of viremia until the host immune response was capable of virus control. Reduction of virus burden early in infection by passive IgG can alter disease outcome in SIV infection of macaques. Modifications of this strategy may lead to effective early treatment of HIV-1 infection in humans.

Original languageEnglish (US)
Pages (from-to)107-114
Number of pages8
JournalImmunology Letters
Volume51
Issue number1-2
DOIs
StatePublished - Jun 1996
Externally publishedYes

Fingerprint

Macaca
Immunoglobulins
Viruses
Infection
Therapeutics
Viremia
Acquired Immunodeficiency Syndrome
Lymph Nodes
Neutralizing Antibodies
Antibodies
Blood Cells
Immunoglobulin G
Virus Diseases
Humoral Immunity
Antigen-Antibody Complex
HIV Infections
Disease Progression
HIV-1
Immune System
Animal Models

Keywords

  • AIDS
  • HIV therapy
  • Humoral immune responses
  • Long term non-progressors
  • Passive antibody therapy
  • Primate lentiviruses
  • RT-QC-PCR
  • SIV/macaque model

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Passive immune globulin therapy in the SIV/macaque model : Early interventisn can alter disease profile. / Haigwood, Nancy; Watson, Andrew; Sutton, William F.; McClure, Jan; Lewis, Anne; Ranchalis, Jane; Travis, Bruce; Voss, Gerald; Letvin, Norman L.; Hu, Shiu Lok; Hirsch, Vanessa M.; Johnson, Philip R.

In: Immunology Letters, Vol. 51, No. 1-2, 06.1996, p. 107-114.

Research output: Contribution to journalArticle

Haigwood, N, Watson, A, Sutton, WF, McClure, J, Lewis, A, Ranchalis, J, Travis, B, Voss, G, Letvin, NL, Hu, SL, Hirsch, VM & Johnson, PR 1996, 'Passive immune globulin therapy in the SIV/macaque model: Early interventisn can alter disease profile', Immunology Letters, vol. 51, no. 1-2, pp. 107-114. https://doi.org/10.1016/0165-2478(96)02563-1
Haigwood, Nancy ; Watson, Andrew ; Sutton, William F. ; McClure, Jan ; Lewis, Anne ; Ranchalis, Jane ; Travis, Bruce ; Voss, Gerald ; Letvin, Norman L. ; Hu, Shiu Lok ; Hirsch, Vanessa M. ; Johnson, Philip R. / Passive immune globulin therapy in the SIV/macaque model : Early interventisn can alter disease profile. In: Immunology Letters. 1996 ; Vol. 51, No. 1-2. pp. 107-114.
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AU - Haigwood, Nancy

AU - Watson, Andrew

AU - Sutton, William F.

AU - McClure, Jan

AU - Lewis, Anne

AU - Ranchalis, Jane

AU - Travis, Bruce

AU - Voss, Gerald

AU - Letvin, Norman L.

AU - Hu, Shiu Lok

AU - Hirsch, Vanessa M.

AU - Johnson, Philip R.

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