Inter-Clade Cross-Reactivity of HIV-1-Specific T Cell Responses in Human Immunodeficiency Virus Type 1 Infection in China

ABSTRACT Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI.

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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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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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Induction of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ and CD4+ T-Cell Reactivity by Dendritic Cells Loaded with HIV-1 X4-Infected Apoptotic Cells

Journal of Virology ◽

10.1128/jvi.76.6.3007-3014.2002 ◽

2002 ◽

Vol 76 (6) ◽

pp. 3007-3014 ◽

Cited By ~ 41

Author(s):

Xiao-Qing Zhao ◽

Xiao-Li Huang ◽

Phalguni Gupta ◽

Luann Borowski ◽

Zheng Fan ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT T-cell responses to X4 strains of human immunodeficiency virus type 1 (HIV-1) are considered important in controlling progression of HIV-1 infection. We investigated the ability of dendritic cells (DC) and various forms of HIV-1 X4 antigen to induce anti-HIV-1 T-cell responses in autologous peripheral blood mononuclear cells from HIV-1-infected persons. Immature DC loaded with HIV-1 IIIB-infected, autologous, apoptotic CD8− cells and matured with CD40 ligand induced gamma interferon production in autologous CD8+ and CD4+ T cells. In contrast, mature DC loaded with HIV-1 IIIB-infected, necrotic cells or directly infected with cell-free HIV-1 IIIB were poorly immunogenic. Thus, HIV-1-infected cells undergoing apoptosis serve as a rich source of X4 antigen for CD8+ and CD4+ T cells by DC. This may be an important mechanism of HIV-1 immunogenicity and provides a strategy for immunotherapy of HIV-1-infected patients on combination antiretroviral therapy.

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Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children

The Journal of Pediatrics ◽

10.1016/s0022-3476(05)80732-2 ◽

1991 ◽

Vol 119 (2) ◽

pp. 230-236 ◽

Cited By ~ 68

Author(s):

Katherine Luzuriaga ◽

Richard A. Koup ◽

Cheryl A. Pikora ◽

Doreen B. Brettler ◽

John L. Sullivan

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

T Cell Responses ◽

Cytotoxic T Cell ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Cytotoxic T Cell Responses

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Higher Homologous and Lower Cross-Reactive Gag-Specific T-Cell Responses in Human Immunodeficiency Virus Type 2 (HIV-2) Than in HIV-1 Infection

Journal of Virology ◽

10.1128/jvi.00027-08 ◽

2008 ◽

Vol 82 (17) ◽

pp. 8619-8628 ◽

Cited By ~ 7

Author(s):

Wim Jennes ◽

Makhtar Camara ◽

Tandakha Dièye ◽

Souleymane Mboup ◽

Luc Kestens

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

T Cell Responses ◽

Cell Responses ◽

Cell Counts ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 2 (HIV-2) infection results in slower CD4+ T-cell decline, lower plasma viral load levels, and hence slower progression of the disease than does HIV-1 infection. Although the reasons for this are not clear, it is possible that HIV-2 replication is more effectively controlled by host responses. We used aligned pools of overlapping HIV-1 and HIV-2 Gag peptides in an enhanced gamma interferon enzyme-linked immunospot assay to compare the levels of homologous and cross-reactive Gag-specific T-cell responses between HIV-1- and HIV-2-infected patients. HIV-2-infected patients showed broader and stronger homologous Gag-specific T-cell responses than HIV-1-infected patients. In contrast, the cross-reactive T-cell responses in HIV-2-infected patients were both narrower and weaker than those in HIV-1-infected patients, in line with overall weaker correlations between homologous and heterologous T-cell responses among HIV-2-infected patients than among HIV-1-infected patients. Cross-reactive responses in HIV-2-infected patients tended to correlate directly with HIV-1/HIV-2 Gag sequence similarities; this was not found in HIV-1-infected patients. The CD4+ T-cell counts of HIV-2-infected patients correlated directly with homologous responses and inversely with cross-reactive responses; this was not found in HIV-1-infected patients. Our data support a model whereby high-level HIV-2-specific T-cell responses control the replication of HIV-2, thus limiting viral diversification and priming of HIV-1 cross-reactive T-cell responses over time. However, we cannot exclude the possibility that HIV-2 replication is controlled by other host factors and that HIV-2-specific T-cell responses are better maintained in the context of slow viral divergence and a less damaged immune system. Understanding the nature of immune control of HIV-2 infection could be crucial for HIV vaccine design.

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