Humoral Responses to Linear Epitopes on the HIV-1 Envelope in Seropositive Volunteers After Vaccine Therapy with rgp 160

Loomis, Lawrence D.; Deal, Carolyn D.; Kersey, Kathryn S.; Burke, Donald S.; Redfield, Robert; Birx, Deborah L.

doi:10.1097/00042560-199509000-00003

Journal of Acquired Immune Deficiency Syndromes & Human Ret

1995

DOI: 10.1097/00042560-199509000-00003

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Humoral Responses to Linear Epitopes on the HIV-1 Envelope in Seropositive Volunteers After Vaccine Therapy with rgp 160

Lawrence D. Loomis

Carolyn D. Deal

Kathryn S. Kersey

et al.

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Cited by 10 publications

(1 citation statement)

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“…Thus, discontinuous epitopes present on the correctly folded proteins, rather than linear epitopes, may be the relevant targets for efficient neutralizing antibodies. Antibodies to such conformational epitopes have been detected in HIV-positive sera (31) but not in vaccinated volunteers (53) in whom immunogens elicit antibodies that recognize linear epitopes, even with diverse specificities, and neutralize TCLA viruses but not PI (3,21).…”

mentioning

confidence: 99%

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition

Spenlehauer

Kirn

Aubertin

et al. 2001

J Virol

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Human immunodeficiency virus type 1 (HIV-1) neutralization occurs when specific antibodies, mainly those directed against the envelope glycoproteins, inhibit infection, most frequently by preventing the entry of the virus into target cells. However, the precise mechanisms of neutralization remain unclear. Previous studies, mostly with cell lines, have produced conflicting results involving either the inhibition of virus attachment or interference with postbinding events. In this study, we investigated the mechanisms of neutralization by immune sera and compared the inhibition of peripheral blood mononuclear cells (PBMC) infection by HIV-1 primary isolates (PI) with the inhibition of T-cell line infection by T-cell line-adapted (TCLA) strains. We followed the kinetics of neutralization to determine at which step of the viral cycle the antibodies act. We found that neutralization of the TCLA strain HIV-1 MN /MT-4 required an interaction between antibodies and cell-free virions before the addition of MT-4 cells, whereas PI were neutralized even after adsorption onto PBMC. In addition, the dose-dependent inhibition of HIV-1 MN binding to MT-4 cells was strongly correlated with serum-induced neutralization. In contrast, neutralizing sera did not reduce the adhesion of PI to PBMC. Postbinding inhibition was also detected for HIV-1 MN produced by and infecting PBMC, demonstrating that the mechanism of neutralization depends on the target cell used in the assay. Finally, we considered whether the different mechanisms of neutralization may reflect the recognition of qualitatively different epitopes on the surface of PI and HIV-1 MN or whether they reflect differences in virus attachment to PBMC and MT-4 cells.

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mentioning

confidence: 99%

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition

Spenlehauer

Kirn

Aubertin

et al. 2001

J Virol

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Correlation between Humoral Responses to Human Immunodeficiency Virus Type 1 Envelope and Disease Progression in Early‐Stage Infection

Loomis-Price

Cox²,

Mascola³

et al. 1998

J INFECT DIS

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Human immunodeficiency virus (HIV)-1-infected rapid and slow progressors showed differential humoral responses against HIV envelope peptides and proteins early in infection. Sera from slow progressors reacted more strongly with short envelope peptides modeling gp160NL4-3, predominantly in gp41. Reactivity to six peptides (in constant regions C3, C4, and C5 of gp120 and in gp41) correlated with slower progression. In a novel association, reactivity to three peptides (in constant regions C1 and C3 and variable region V3 of gp120) correlated with faster progression. Envelope peptide reactivity correlated with subsequent course of disease progression as strongly as did reactivity to gag p24. Patients heterozygous for 32-bp deletions in the CCR5 coreceptor reacted more frequently to an epitope in gp41. Rapid progressors had greater gp120 native-to-denatured binding ratios than did slow progressors. While antibody-dependent cellular cytotoxicity against gp120 did not strongly differentiate the groups, slow progressors showed a broader neutralization pattern against 5 primary virus isolates.

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Preliminary Evaluation of Human Immunodeficiency Virus Type 1 (HIV‐1) Immunogen in Children with HIV‐1 Infection

et al. 1999

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The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2. 5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log10 HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n=4] vs. 2.5 U [n=3], respectively; P=.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P<.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.

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Humoral Responses to Linear Epitopes on the HIV-1 Envelope in Seropositive Volunteers After Vaccine Therapy with rgp 160

Cited by 10 publications

References 0 publications

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition

Correlation between Humoral Responses to Human Immunodeficiency Virus Type 1 Envelope and Disease Progression in Early‐Stage Infection

Preliminary Evaluation of Human Immunodeficiency Virus Type 1 (HIV‐1) Immunogen in Children with HIV‐1 Infection

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