scholarly journals Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1324
Author(s):  
Kimberly Braz Gomes ◽  
Sucheta D’Sa ◽  
Grace Lovia Allotey-Babington ◽  
Sang-Moo Kang ◽  
Martin J. D’Souza
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Influenza A ◽  
Lipid A ◽  
Adaptive Immune ◽  
Monophosphoryl Lipid A ◽  
Virus Like Particle ◽  
The Matrix ◽  
A Cell ◽  
Potential Vaccine

In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel® and Monophosphoryl Lipid-A (MPL-A®), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4+ T cells in the spleen and the lymph node and high levels of CD8+ T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine.

scholarly journals A cell-extrinsic ligand acquired by activated T cells in lymph node can bridge L-selectin and P-selectin

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205685 ◽  
Author(s):  
Douglas A. Carlow ◽  
Michelle C. Tra ◽  
Hermann J. Ziltener
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Activated T Cells ◽  
A Cell

scholarly journals Parenterally Administered Norovirus GII.4 Virus-Like Particle Vaccine Formulated with Aluminum Hydroxide or Monophosphoryl Lipid A Adjuvants Induces Systemic but Not Mucosal Immune Responses in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Suvi Heinimäki ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Aluminum Hydroxide ◽  
Mucosal Immunity ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Virus Like Particle ◽  
Iga Antibodies ◽  
Nasal Secretions ◽  
Sparing Effect ◽  
Norovirus Gii

Norovirus (NoV) is a main cause of acute gastroenteritis across all ages worldwide. NoV vaccine candidates currently in clinical trials are based on noninfectious highly immunogenic virus-like particles (VLPs) delivered intramuscularly (IM). Since NoV is an enteric pathogen, it is likely that mucosal immunity has a significant role in protection from infection in the intestine. Due to the fact that IM delivery of NoV VLPs does not generate mucosal immunity, we investigated whether NoV genotype GII.4 VLPs coadministered with aluminum hydroxide (Al(OH)3) or monophosphoryl lipid A (MPLA) would induce mucosal antibodies in mice. Systemic as well as mucosal IgG and IgA antibodies in serum and intestinal and nasal secretions were measured. As expected, strong serum IgG, IgG1, and IgG2a antibodies as well as a dose sparing effect were induced by both Al(OH)3and MPLA, but no mucosal IgA antibodies were detected. In contrast, IN immunization with GII.4 VLPs without an adjuvant induced systemic as well as mucosal IgA antibody response. These results indicate that mucosal delivery of NoV VLPs is needed for induction of mucosal responses.

scholarly journals Adaptive and innate immune cell responses in tendons and lymph nodes after tendon injury and repair

2020 ◽  
Vol 128 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Andrew C. Noah ◽  
Thomas M. Li ◽  
Leandro M. Martinez ◽  
Susumu Wada ◽  
Jacob B. Swanson ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Immune System ◽  
Innate Immune System ◽  
Immune Cell ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Immune Cell Response

Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate immune system, such as neutrophils and macrophages, have been studied in tendon injuries. However, the adaptive immune system, comprising specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues, but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we determined how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month-old male mice. We observed that lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons, and that the lymphatics drain into the popliteal lymph node. We then created an acute Achilles tenotomy followed by repair, and collected tendons and popliteal lymph nodes 1, 2, and 4 wk after injury. Tendon injury resulted in a robust adaptive immune cell response that followed an initial innate immune cell response in tendons and lymph nodes. Monocytes, neutrophils, and macrophages initially accumulated at 1 wk after injury in tendons, while dendritic cells and CD4+ T cells peaked at 2 wk after injury. B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury, and adaptive immune cells may play a role in regulating tendon healing. NEW & NOTEWORTHY While the innate immune system, consisting of macrophages and related hematopoietic cells, has been studied in tendon injury, less is known about the adaptive immune system. Using a mouse model of Achilles tendon tenotomy and repair, we observed an adaptive immune cell response, consisting of CD4+ and CD8+ T cells, and B cells, which occur through 4 wk after tendon injury. This response appeared to be coordinated by the draining popliteal lymph node.

scholarly journals Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 204 ◽  
Author(s):  
Bassel Akache ◽  
Lise Deschatelets ◽  
Blair A. Harrison ◽  
Renu Dudani ◽  
Felicity C. Stark ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Lipid A ◽  
Cellular Responses ◽  
Current Treatment ◽  
Water Emulsion ◽  
Treatment Regimens ◽  
Immune Parameters ◽  
Monophosphoryl Lipid A ◽  
Oil In Water Emulsion

Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested.

scholarly journals Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4+ T Cells

2016 ◽  
Vol 7 ◽  
Author(s):  
Jaxaira Maggi ◽  
Katina Schinnerling ◽  
Bárbara Pesce ◽  
Catharien M. Hilkens ◽  
Diego Catalán ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Memory Cd4 T Cells

scholarly journals Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs

2007 ◽  
Vol 205 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Andrea J. Wolf ◽  
Ludovic Desvignes ◽  
Beth Linas ◽  
Niaz Banaiee ◽  
Toshiki Tamura ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Lymph Node ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Initial Activation ◽  
Local Lymph Node

The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.

scholarly journals Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity

2020 ◽  
Author(s):  
Diana H. Quan ◽  
Claudio Counoupas ◽  
Gayathri Nagalingam ◽  
Rachel Pinto ◽  
Nikolai Petrovsky ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Protective Effect ◽  
Lipid A ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
List Type ◽  
Vaccination Site ◽  
Monophosphoryl Lipid A ◽  
Vaccine Site

AbstractThe development of safe and effective adjuvants is a critical goal of vaccine development programs. In this report, we defined the immunostimulatory profile and protective effect against aerosol Mycobacterium tuberculosis infection of vaccine formulations incorporating the semi-crystalline adjuvant δ-inulin (Advax). Advax formulated with CpG oligonucleotide and the QS-21 saponin (AdvaxCpQS) was the most effective combination, demonstrated by the capacity of CysVac2/AdvaxCpQS to significantly reduce the bacterial burden in the lungs of M. tuberculosis-infected mice. CysVac2/AdvaxCpQS protection was associated with rapid influx of neutrophils, macrophages and monocytes to the site of vaccination and the induction of antigen-specific IFN-γ+/IL-2+/TNF+ polyfunctional CD4+ T cells in the lung. When compared to the highly potent adjuvant combination of monophosphoryl lipid A and dimethyldioctadecylammonium bromide (MPL/DDA), AdvaxCpQS imparted a similar level of protective efficacy yet without the profound stimulation of inflammatory cytokines and vaccination site ulceration observed with MPL/DDA. Addition of DDA to CysVac2/ AdvaxCpQS further improved the protective effect of the vaccine, which correlated with increased polyfunctional CD4+ T cells in the lung but with no increase in vaccine reactogenicity. The data demonstrate that Advax formulations can decouple protective tuberculosis immunity from reactogenicity, making them ideal candidates for human application.HighlightsAdvax adjuvant formulations improve pulmonary protection against aerosol Mycobacterium tuberculosis infectionDifferent combinations of adjuvant components markedly influence the level of protection observedProtection is associated with the rapid influx of myeloid cells to the site of vaccination and the induction of antigen-specific polyfunctional CD4+ T cells in the lung.Advax formulations abrogate vaccine-site ulceration and inflammatory cytokine production

scholarly journals Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin

2019 ◽  
Vol 216 (7) ◽  
pp. 1487-1496 ◽  
Author(s):  
Brian J. Laidlaw ◽  
Elizabeth E. Gray ◽  
Yang Zhang ◽  
Francisco Ramírez-Valle ◽  
Jason G. Cyster
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Γδ T Cells ◽  
Dependent Manner ◽  
Γδ T Cell ◽  
T Cell Migration ◽  
Sphingosine 1 Phosphate ◽  
A Cell ◽  
Draining Lymph Node

Maintenance of a population of IL-17–committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1-phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17+ γδ T cells establish residence within the dermis and identify a role for S1PR2 in restraining the egress of tissue-resident lymphocytes.

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