Systemic mobilization of antigen presenting cells, with a chimeric Flt-3 and G-CSF receptor agonist, during immunization of with HIV-1 antigens is insufficient to modulate immune responses or vaccine efficacy

Abstract Recombinant Mycobacterium strains such as recombinant BCG (rBCG) have received considerable attention for the HIV-1 vaccine development. Recently, we described a temperature-sensitive Mycobacterium paragordonae (Mpg) strain as a novel live tuberculosis vaccine that is safer and showed an enhanced protective effect against mycobacterial infection compared to BCG. We studied the possibility of developing a vaccine against HIV-1 infection using rMpg strain expressing the p24 antigen (rMpg-p24). We observed that rMpg-p24 can induce an increased p24 expression in infected antigen presenting cells (APCs) compared to rBCG-p24. We also observed that rMpg-p24 can induce enhanced p24 specific immune responses in vaccinated mice as evidenced by increased p24-specific T lymphocyte proliferation, gamma interferon induction, antibody production and cytotoxic T lymphocyte (CTL) responses. Furthermore, an rMpg-p24 prime and plasmid DNA boost showed an increased CTL response and antibody production compared to rBCG or rMpg alone. In summary, our study indicates that a live rMpg-p24 strain induced enhanced immune responses against HIV-1 Gag in vaccinated mice. Thus, rMpg-p24 may have potential as a preventive prime vaccine in a heterologous prime-boost regimen for HIV-1 infection.

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HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

Scientifica ◽

10.1155/2013/164203 ◽

2013 ◽

Vol 2013 ◽

pp. 1-30 ◽

Cited By ~ 15

Author(s):

Charles R. Rinaldo

Keyword(s):

T Cells ◽

Virus Replication ◽

Virus Transmission ◽

Antigen Presenting Cells ◽

Activated T Cells ◽

Infection Processes ◽

The Many ◽

Antigen Presenting ◽

Hiv 1 ◽

Virus Subtype

Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1transinfection of CD4+T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct,cisinfection of either APC or T cells, ortransinfection between T cells. Such APC-to-T celltransinfection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of thesetransinfection processes and their role in natural HIV-1 infection.

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Antibody Inhibition of HIV-1 Transmission from Antigen-presenting Cells to CD4 T Lymphocytes Involves Immune Cell Activation

AIDS Research and Human Retroviruses ◽

10.1089/aid.2014.5316.abstract ◽

2014 ◽

Vol 30 (S1) ◽

pp. A154-A154

Author(s):

Bin Su ◽

Alexandre Lederle ◽

Géraldine Laumond ◽

Sylvie Schmidt ◽

Thomas Decoville ◽

...

Keyword(s):

T Lymphocytes ◽

Cell Activation ◽

Immune Cell ◽

Antigen Presenting Cells ◽

Immune Cell Activation ◽

Antigen Presenting ◽

Antibody Inhibition ◽

Hiv 1

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Interactions of HIV-1 with antigen-presenting cells

Immunology and Cell Biology ◽

10.1046/j.1440-1711.1999.00833.x ◽

1999 ◽

Vol 77 (4) ◽

pp. 289-303 ◽

Cited By ~ 6

Author(s):

Tim Hewson ◽

Nazir Lone ◽

Marilyn Moore ◽

Sarah Howie

Keyword(s):

Antigen Presenting Cells ◽

Antigen Presenting ◽

Hiv 1

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Altered Humoral Immune Responses and IgG Subtypes in NOX2-Deficient Mice and Patients: A Key Role for NOX2 in Antigen-Presenting Cells

Frontiers in Immunology ◽

10.3389/fimmu.2018.01555 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Julien Cachat ◽

Christine Deffert ◽

Marco Alessandrini ◽

Pascale Roux-Lombard ◽

Audrey Le Gouellec ◽

...

Keyword(s):

Immune Responses ◽

Antigen Presenting Cells ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Presenting ◽

Deficient Mice

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Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells

Blood ◽

10.1182/blood-2007-09-113522 ◽

2008 ◽

Vol 111 (7) ◽

pp. 3546-3552 ◽

Cited By ~ 33

Author(s):

Christian Schütz ◽

Martin Fleck ◽

Andreas Mackensen ◽

Alessia Zoso ◽

Dagmar Halbritter ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Fas Ligand ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cytotoxic T Cell ◽

Cell Responses ◽

Cytotoxic T Cell Responses ◽

Antigen Presenting

Abstract Several cell-based immunotherapy strategies have been developed to specifically modulate T cell–mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell–based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)–dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of κaAPCs and independent of activation-induced cell death (AICD). κaAPCs represent a novel technology that can control T cell–mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.

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