scholarly journals Potent Immune Response against HIV-1 and Protection from Virus Challenge in hu-PBL-SCID Mice Immunized with Inactivated Virus-pulsed Dendritic Cells Generated in the Presence of IFN-α

2003 ◽  
Vol 198 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Caterina Lapenta ◽  
Stefano M. Santini ◽  
Mariantonia Logozzi ◽  
Massimo Spada ◽  
Mauro Andreotti ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Vaccine ◽  
Vaccination Schedule ◽  
T Cell Response ◽  
Scid Mice ◽  
Virus Challenge ◽  
Gm Csf ◽  
Human Immune Response ◽  
Anti Hiv ◽  
Hiv 1

A major challenge of AIDS research is the development of therapeutic vaccine strategies capable of inducing the humoral and cellular arms of the immune responses against HIV-1. In this work, we evaluated the capability of DCs pulsed with aldrithiol-2–inactivated HIV-1 in inducing a protective antiviral human immune response in SCID mice reconstituted with human PBL (hu-PBL-SCID mice). Immunization of hu-PBL-SCID mice with DCs generated after exposure of monocytes to GM-CSF/IFN-α (IFN-DCs) and pulsed with inactivated HIV-1 resulted in a marked induction of human anti–HIV-1 antibodies, which was associated with the detection of anti-HIV neutralizing activity in the serum. This vaccination schedule also promoted the generation of a human CD8+ T cell response against HIV-1, as measured by IFN-γ Elispot analysis. Notably, when the hu-PBL-SCID mice immunized with antigen-pulsed IFN-DCs were infected with HIV-1, inhibition of virus infection was observed as compared with control animals. These results suggest that IFN-DCs pulsed with inactivated HIV-1 can represent a valuable approach of immune intervention in HIV-1–infected patients.

scholarly journals Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice

2000 ◽  
Vol 191 (10) ◽  
pp. 1777-1788 ◽  
Author(s):  
Stefano M. Santini ◽  
Caterina Lapenta ◽  
Mariantonia Logozzi ◽  
Stefania Parlato ◽  
Massimo Spada ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cell ◽  
Scid Mice ◽  
Primary Immune Response ◽  
Type I ◽  
Antitumor Effects ◽  
Gm Csf ◽  
Type I Ifns ◽  
Hiv 1

Type I interferons (IFNs) are cytokines exhibiting antiviral and antitumor effects, including multiple activities on immune cells. However, the importance of these cytokines in the early events leading to the generation of an immune response is still unclear. Here, we have investigated the effects of type I IFNs on freshly isolated granulocyte/macrophage colony-stimulating factor (GM-CSF)–treated human monocytes in terms of dendritic cell (DC) differentiation and activity in vitro and in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) mice. Type I IFNs induced a surprisingly rapid maturation of monocytes into short-lived tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)–expressing DCs endowed with potent functional activities, superior with respect to the interleukin (IL)-4/GM-CSF treatment, as shown by FACS® analyses, mixed leukocyte reaction assays with allogeneic PBLs, and lymphocyte proliferation responses to HIV-1–pulsed autologous DCs. Type I IFN induced IL-15 production and strongly promoted a T helper cell type 1 response. Notably, injection of IFN-treated HIV-1–pulsed DCs in SCID mice reconstituted with autologous PBLs resulted in the generation of a potent primary immune response, as evaluated by the detection of human antibodies to various HIV-1 antigens. These results provide a rationale for using type I IFNs as vaccine adjuvants and support the concept that a natural alliance between these cytokines and monocytes/DCs represents an important early mechanism for connecting innate and adaptive immunity.

Human Immune Response to a Peptide Mimic ofNeisseria meningitidisSerogroup C in hu-PBMC-SCID Mice

Hybridoma ◽  
1999 ◽  
Vol 18 (2) ◽  
pp. 121-129 ◽  
Author(s):  
WENDY A. HUTCHINS ◽  
THOMAS KIEBER-EMMONS ◽  
GEORGE M. CARLONE ◽  
M.A. JULIE WESTERINK
Keyword(s):  
Immune Response ◽  
Scid Mice ◽  
Peptide Mimic ◽  
Human Immune Response ◽  
Human Immune

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

Booster immunization of HIV-1 negative volunteers with HGP-30 vaccine induces protection against HIV-1 virus challenge in SCID mice

Vaccine ◽  
1999 ◽  
Vol 17 (1) ◽  
pp. 64-71 ◽  
Author(s):  
P.S Sarin ◽  
J.E Talmadge ◽  
P Heseltine ◽  
N Murcar ◽  
H.E Gendelman ◽  
...  
Keyword(s):  
Scid Mice ◽  
Booster Immunization ◽  
Virus Challenge ◽  
Hiv 1

REVIEW OF HIV MODELS: THE ROLE OF THE NATURAL IMMUNE RESPONSE AND IMPLICATIONS FOR TREATMENT

2004 ◽  
Vol 12 (02) ◽  
pp. 123-135 ◽  
Author(s):  
REBECCA V. CULSHAW
Keyword(s):  
Immune Response ◽  
Optimal Treatment ◽  
Minimal Cost ◽  
Treatment Scenario ◽  
Forcing Function ◽  
Drug Regimens ◽  
Differential Equations Models ◽  
Anti Hiv ◽  
Hiv 1

We present a review and comparison of several recent differential equations models of treatment of HIV-1 infection. We seek to clarify the role of the natural anti-HIV immune response and determine its effect upon optimal treatment schemes. In this paper, we consider systems in which treatment is expressed as a forcing function, as well as those in which we determine optimal treatment via control theoretic techniques. The primary goal of this study is to compare treatment schemes for systems in which a natural nonconstant immune response of the patient is considered explicitly with those that consider implicitly a constant non-specific immune response. We find that when the natural immune response can be boosted sufficiently, drug levels may not need to be as high as previously supposed. This implies that a treatment scenario in which intervals of drug treatment are alternated with some form of immune-boosting therapy may be highly beneficial in terms of reducing toxicity to the patient. Additionally, in developing countries where HIV infection is widespread and sufficient funds are not available to supply rigourous drug regimens, the implications of these models are profound, as they suggest methods of treating HIV at a minimal cost.

Clonal Patterns in the Human Immune Response to HIV-1 Infection

1992 ◽  
Vol 9 (1) ◽  
pp. 1-13 ◽  
Author(s):  
S. Müller ◽  
P. Nara ◽  
R. D'amelio ◽  
R. Biselli ◽  
D. Gold ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immune Response ◽  
Human Immune ◽  
Hiv 1

scholarly journals Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

2020 ◽  
Vol 9 (8) ◽  
pp. 2452
Author(s):  
Rubén Ayala-Suárez ◽  
Francisco Díez-Fuertes ◽  
Esther Calonge ◽  
Humberto Erick De La Torre Tarazona ◽  
María Gracia-Ruíz de Alda ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Elite Controllers ◽  
Peripheral Blood Mononuclear ◽  
Extreme Phenotypes ◽  
Blood Mononuclear Cells ◽  
Before And After ◽  
Anti Hiv ◽  
Hiv 1

Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.

Effect of granulocyte-macrophage colony stimulating factor (GM-CSF) administered with a multipeptide vaccine on circulating CD8+ and CD4+ T-cell responses: Outcome of a multicenter randomized trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3008-3008
Author(s):  
C. L. Slingluff ◽  
G. R. Petroni ◽  
W. C. Olson ◽  
M. E. Smolkin ◽  
M. I. Ross ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Clinical Outcome ◽  
T Cell Responses ◽  
Response Rates ◽  
T Cell Response ◽  
Gm Csf ◽  
Cell Responses ◽  
Helper Peptide

3008 Background: GM-CSF administered locally with vaccines can augment T-cell responses in animal models. Human experience with GM-CSF has mostly occurred in uncontrolled or nonrandomized trials. Thus, a multicenter prospective randomized phase II trial was performed to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine administered in an emulsion with an incomplete Freund's adjuvant (IFA). A second component of the trial was designed to assess whether the vaccine administered in two sites is more immunogenic than in a single site. Methods: 121 eligible and evaluable patients with resected stage IIB-IV melanoma were administered a sequence of multipeptide vaccines, each consisting of 12 MHC Class I-restricted melanoma peptides (12MP) to stimulate CD8+ T cells, plus an HLA-DR restricted tetanus helper peptide to stimulate CD4+ T cells. Peptides were emulsified with IFA, with or without GM-CSF. T cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis, weekly x 8. Clinical outcome was evaluated for all patients. Results: Vaccination was well-tolerated, and each peptide was immunogenic. Overall CD8+ T-cell response rates to the 12MP (days 1–50), for patients vaccinated with or without GM-CSF were 43% and 75%, respectively (p < 0.001), and response magnitude was almost twice as high in patients without GM-CSF. Class I MHC tetramer analyses corroborated the functional data. There was also a greater CD4+ T-cell response to the tetanus helper peptide without GM-CSF than with it (95% and 77%, respectively, p = 0.005). There was no significant difference in immune response rates by the number of vaccine sites. For the entire patient group, 3-year overall and disease-free survival estimates [95% CI] were 76% [67, 83%] and 52% [43, 61%], respectively. There have been too few events to assess differences in clinical outcome by study arm. Conclusions: High immune response rates were achieved with this multipeptide vaccine, but CD8+ and CD4+ T-cell responses appear to be partially suppressed with addition of GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. [Table: see text]

Therapeutic vaccination against HIV: current progress and future possibilities

2005 ◽  
Vol 110 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Rebekah L. Puls ◽  
Sean Emery
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Vectors ◽  
Therapeutic Vaccine ◽  
Viral Disease ◽  
Clear Understanding ◽  
Therapeutic Vaccination ◽  
Expensive Drug ◽  
Drug Regimens ◽  
Anti Hiv ◽  
Hiv 1

Although effective in reducing mortality, current antiretroviral therapy for HIV infection involves complex and expensive drug regimens that are toxic and difficult to take. Eradication of HIV reservoirs is not possible with existing therapies. The concept of therapeutic vaccination has been investigated to increase the potency and breadth of anti-HIV immune responses in order to delay or reduce antiretroviral therapy use. A variety of approaches targeted to both cell- and antibody-mediated immunity have been developed, including whole inactivated HIV-1, protein subunits and synthetic peptides, DNA vaccines and a number of viral vectors expressing HIV-1. These investigations have occurred in the absence of a clear understanding of disease pathogenesis or the correlates of protective immunity. At this time, there is no licensed therapeutic vaccine for any viral disease, including HIV; however, this review will consider recent progress in the field and summarize the challenges faced in the development of a therapeutic HIV vaccine.

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