Immunopotentiation of the humoral response by liposomes: Effect of a T cell polyclonal activator

1988 ◽  
Vol 116 (2) ◽  
pp. 320-330 ◽  
Author(s):  
Hélène-Marie Thérien ◽  
Eliane Shahum
Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 606
Author(s):  
Giuseppe Cappellano ◽  
Hugo Abreu ◽  
Chiara Casale ◽  
Umberto Dianzani ◽  
Annalisa Chiocchetti

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.


1992 ◽  
Vol 60 (9) ◽  
pp. 3579-3585 ◽  
Author(s):  
J Katz ◽  
R M Leary ◽  
D C Ward ◽  
C C Harmon ◽  
S M Michalek

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Kisha Nandini Sivanathan ◽  
Darling Rojas-Canales ◽  
Shane T. Grey ◽  
Stan Gronthos ◽  
Patrick T. Coates

Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3031-3031
Author(s):  
S. Parker ◽  
D. Berman ◽  
K. L. Bennett ◽  
S. Alaparthy ◽  
Z. Tsuchihashi ◽  
...  

3031 Background: Ipilimumab is an anti-CTLA-4 monoclonal antibody (Ab) that overcomes T-cell suppression. In this phase II study (CA184004), humoral and cellular responses were assessed in ipilimumab-treated pts with unresectable stage III/IV melanoma. Methods: Ipilimumab 3 or 10 mg/kg was given every 3 weeks x 4. Tetanus boosters were given ≤10 days pre-treatment. Influenza and pneumococcal vaccines were given 5 days after first ipilimumab dose. Tetanus, anti-influenza, and anti-pneumococcal Ab levels were assessed at pre-dose and Wk 7. Humoral response to 5 tumor antigens (Ag) and a control Ag (DHFR) were examined at baseline (BL) and at Wks 4, 8–9, and 12. DTH skin tests were given at pre-dose and Wk 4, with responses recorded 15 minutes (min) and 24–72 hours (hrs) post-test. Peripheral T-cell populations were evaluated through flow cytometry at BL, Wk 4, and Wk 12. Results: Pts received ipilimumab 3 (n = 40) or 10 mg/kg (n = 42). Increases from BL in humoral responses to pneumococcal (40–50/78 pts, depending on Ab) and tetanus (58/78 pts) vaccines were noted, even in pts who did not receive on-study pneumococcal (4–9 pts) or tetanus (7 pts) vaccines. Increased humoral response to influenza only occurred in pts receiving the influenza vaccine. Maximum increase from BL of ≥ 5-fold titer (clinically meaningful threshold) in humoral response to tumor Ag MELANA (23.2% of pts), SSX2 (20.3%), NYES01 (18.8%), MAGEA4 (10.1%), and P53 (4.3%) (DHFR, 4.3%) was noted without tumor vaccines. Tumor Ag response was not associated with clinical activity (complete or partial response, or stable disease ≥ 24 wks). Increased DTH reactions were noted for tetanus, 24–72 hrs (3 mg/kg: 5/7 pts; 10 mg/kg: 3/6 pts); tuberculin, 15 min (3 mg/kg: 7/15 pts; 10 mg/kg: 4/15 pts); Candida, 15 min (3 mg/kg: 4/6 pts; 10 mg/kg: 2/7 pts); and Trichophyton, 15 min (3 mg/kg: 3/4 pts; 10 mg/kg: 2/5 pts). Significant increases from BL in percents of HLA-DR+ CD4+ (p = 9.3x10-7), HLA-DR+ CD8+ (p = 0.018), and ICOS+ CD4+ (p = 0.0027) effector T cells were noted. Conclusions: Humoral immunity in ipilimumab-treated pts increased (± vaccination) in an Ag-dependent manner and cellular immunity was enhanced. Change in tumor Ag response was not associated with clinical activity. [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2528-2528
Author(s):  
Kieron Dunleavy ◽  
Sattva Swarup Neelapu ◽  
Larry W. Kwak ◽  
Cliona Grant ◽  
Carlos F. Santos ◽  
...  

2528 Background: Murine models show Id-vaccines induce antitumor responses, possibly through Th1/Tc1 cytokines. We report an 11-year follow-up of Id-vaccine following DA-EPOCH-Rituximab in 26 untreated MCL patients. Methods: DA-EPOCH-R was administered q3 weeks × 6, followed 12 weeks later by 5 cycles of Id-vaccine. Id protein was made by hybridoma technology, conjugated to keyhole limpet hemocyanin (KLH) and administered with GM-CSF. Pre- and post-vaccine immune responses (IR) were tested in parallel: anti-Id and anti-KLH humoral responses (ELISA); anti-KLH cellular responses (intracellular cytokine assay); and anti-tumor cellular responses (cytokine induction, IFNγ ELISPOT). Results: Characteristics: median age 57 (r 22-73), blastoid variant 15%, and MIPI (low-65%; intermediate-16%; high-19%). With 122 mo median follow-up (r 111-132), the median PFS is 24 mo and OS is 104 mo. MIPI was associated with OS (p=0.0002); median OS: low (not reached), intermediate (84 mo) and high (44 mo). We found no association between OS and anti-KLH IR, anti-Id humoral response, IFNγ ELISPOT, or antitumor TNFα or IFNγ responses. Normalized antitumor T-cell GM-CSF response (median <4.3 vs. >4.3) was associated with OS of 79 mo vs. not reached, respectively (p=0.015 (unadj.) and p=0.045 (adj.)). MIPI (p=0.02) and GM-CSF (p=0.057) were independently associated with OS. TTNT (based on disease activity), correlated with antitumor GM-CSF response (p=0.018) but not MIPI and was independent of MIPI (GM-CSF; p=0.041). Correlation of pre-and post-treatment GM-CSF production suggested a priming effect. Tumor proliferation by GEP did not correlate with OS (n=14). Conclusions: Antitumor GM-CSF response was significantly associated with OS and TTNT, suggesting antitumor cellular immune response significantly delayed tumor growth. Antitumor GM-CSF response may serve as a surrogate biomarker for vaccine efficacy. Our results are consistent with recent data that T-cell GM-CSF production is required for breaking tolerance against self-antigens. Id vaccines may prolong survival of MCL following rituximab-based chemotherapy and should be further evaluated.


Vaccine ◽  
2001 ◽  
Vol 20 (5-6) ◽  
pp. 731-736 ◽  
Author(s):  
Flávia W. da Cruz ◽  
Alan J.A. McBride ◽  
Fabrı́cio R. Conceição ◽  
Jeremy W. Dale ◽  
Johnjoe McFadden ◽  
...  

2001 ◽  
Vol 31 (8) ◽  
pp. 2266-2276 ◽  
Author(s):  
Magali Savignac ◽  
Abdallah Badou ◽  
Christelle Delmas ◽  
Jean-François Subra ◽  
Stéphane De Cramer ◽  
...  
Keyword(s):  
T Cell ◽  

Author(s):  
Moraima Jiménez ◽  
Elisa Roldan ◽  
Candela Fernández- Naval ◽  
Guillermo Villacampa ◽  
Monica Martinez-Gallo ◽  
...  

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.


2019 ◽  
Vol 17 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fatemeh Tohidi ◽  
Seyed Mehdi Sadat ◽  
Azam Bolhassani ◽  
Ramin Yaghobi ◽  
Mona Sadat Larijani

Background: Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. Objective: This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. Methods: Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. Results: The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. Conclusion: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.


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