Detection of Human Immunodeficiency Virus Type 1 Envelope Peptide- Stimulated T-helper Cell Responses and Variations in the Corresponding Regions of Viral Isolates among Vertically Infected Children

ABSTRACT The discovery of multiple subtypes of human immunodeficiency virus type 1 (HIV-1) worldwide has created new challenges for the development of both therapeutic and preventive AIDS vaccines. We examined T-helper proliferative responses to HIV-1 clade A, B, C, G, and E whole-killed virus and to HIV-1 clade G and B core (p24) antigens in HIV-1-infected subjects taking potent antiviral drugs who received HIV immunogen (Remune) therapeutic vaccination. Subjects who were immunized mounted strong proliferative responses to both whole virus and core antigens of the different clades. These results suggest that a whole-killed immunogen may have broad applications as a therapeutic as well as a preventive vaccine in the current multiclade HIV-1 pandemic.

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A factor from CD8 cells of human immunodeficiency virus-infected patients suppresses HLA self-restricted T helper cell responses.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.89.18.8424 ◽

1992 ◽

Vol 89 (18) ◽

pp. 8424-8428 ◽

Cited By ~ 9

Author(s):

M. Clerici ◽

E. Roilides ◽

C. S. Via ◽

P. A. Pizzo ◽

G. M. Shearer

Keyword(s):

Human Immunodeficiency Virus ◽

T Helper Cell ◽

Helper Cell ◽

T Helper ◽

Cd8 Cells ◽

Cell Responses ◽

Immunodeficiency Virus

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Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

Journal of General Virology ◽

10.1099/vir.0.80481-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 349-354 ◽

Cited By ~ 35

Author(s):

Eva K. L. Nordström ◽

Mattias N. E. Forsell ◽

Christina Barnfield ◽

Eivor Bonin ◽

Tomas Hanke ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Dna Vaccine ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Semliki Forest Virus ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

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Human Immunodeficiency Virus Type 1 Evades T-Helper Responses by Exploiting Antibodies That Suppress Antigen Processing

Journal of Virology ◽

10.1128/jvi.78.14.7645-7652.2004 ◽

2004 ◽

Vol 78 (14) ◽

pp. 7645-7652 ◽

Cited By ~ 15

Author(s):

Peter C. Chien ◽

Sandra Cohen ◽

Michael Tuen ◽

James Arthos ◽

Pei-de Chen ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Antigen Processing ◽

T Helper ◽

Peptide Epitopes ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT T-helper responses are important for controlling chronic viral infections, yet T-helper responses specific to human immunodeficiency virus type 1 (HIV-1), particularly to envelope glycoproteins, are lacking in the vast majority of HIV-infected individuals. It was previously shown that the presence of antibodies to the CD4-binding domain (CD4bd) of HIV-1 glycoprotein 120 (gp120) prevents T-helper responses to gp120, but their suppressive mechanisms were undefined (C. E. Hioe et al., J. Virol. 75:10950-10957, 2001). The present study demonstrates that gp120, when complexed to anti-CD4bd antibodies, becomes more resistant to proteolysis by lysosomal enzymes from antigen-presenting cells such that peptide epitopes are not released and presented efficiently by major histocompatibility complex class II molecules to gp120-specific CD4 T cells. Antibodies to other gp120 regions do not confer this effect. Thus, HIV may evade anti-viral T-helper responses by inducing and exploiting antibodies that conceal the virus envelope antigens from T cells.

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Induction of Potent CD8+ T-Cell Responses by Novel Biodegradable Nanoparticles Carrying Human Immunodeficiency Virus Type 1 gp120

Journal of Virology ◽

10.1128/jvi.00489-07 ◽

2007 ◽

Vol 81 (18) ◽

pp. 10009-10016 ◽

Cited By ~ 45

Author(s):

Xin Wang ◽

Tomofumi Uto ◽

Takami Akagi ◽

Mitsuru Akashi ◽

Masanori Baba

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Memory T Cells ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, γ-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, γ-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses.

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Potentially Exposed but Uninfected Individuals Produce Cytotoxic and Polyfunctional Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Which Can Be Defined to the Epitope Level

Clinical and Vaccine Immunology ◽

10.1128/cvi.00247-08 ◽

2008 ◽

Vol 15 (11) ◽

pp. 1745-1748 ◽

Cited By ~ 27

Author(s):

A. L. Erickson ◽

C. B. Willberg ◽

V. McMahan ◽

A. Liu ◽

S. P. Buchbinder ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cytotoxic T Lymphocyte ◽

T Cell Responses ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Sex With Men

ABSTRACT We measured CD8+ T-cell responses in 12 potentially exposed but uninfected men who have sex with men by using cytokine flow cytometry. Four of the individuals screened exhibited polyfunctional immune responses to human immunodeficiency virus type 1 Gag or Vif. The minimum cytotoxic T lymphocyte epitope was mapped in one Gag responder.

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