3M‐052 as an adjuvant for a PLGA microparticle‐based <i>Leishmania donovani</i> recombinant protein vaccine

Wang, Qian; Barry, Meagan A.; Seid, Christopher A.; Hudspeth, Elissa M.; McAtee, C. Patrick; Heffernan, Michael J.

doi:10.1002/jbm.b.33965

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…Such studies also would address the duration of the protective response following ChimeraT/liposome vaccination and whether vaccination induces antigen-specific serum IgE antibodies. Although we and others have used qualitative ELISA to measure serum antibody levels [ 51 , 76 , 77 , 78 , 79 ], quantitative measurements of antibody levels in both mouse and human sera and examination of antigen-specific T-cell proliferative responses in cell culture would further inform the nature of the immune responses. Additionally, the parasite load could be evaluated by examining any histopathological changes in the organs and correlated with data obtained by the limiting dilution technique and RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

et al. 2020

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Background: Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are no human vaccines in use routinely. The purpose of this study was to examine the immunogenicity of ChimeraT, a novel synthetic recombinant vaccine against visceral leishmaniasis (VL), incorporated into a human-compatible liposome formulation. Methods: BALB/c mice were immunized subcutaneously with ChimeraT/liposome vaccine, ChimeraT/saponin adjuvant, or ChimeraT/saline and immune responses examined in vitro and in vivo. Results: Immunization with the ChimeraT/liposome formulation induced a polarized Th1-type response and significant protection against L. infantum infection. ChimeraT/liposome vaccine stimulated significantly high levels of interferon (IFN)-γ, interleukin (IL)-12, and granulocyte macrophage-colony stimulating factor (GM-CSF) cytokines by both CD4 and CD8 T-cells, with correspondingly lower levels of IL-4 and IL-10 cytokines. Induced antibodies were predominantly IgG2a isotype, and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide (NO). Furthermore, we examined a small number of treated VL patients and found higher levels of circulating anti-ChimeraT protein IgG2 antibodies, compared to IgG1 levels. Conclusions: Overall, the liposomal formulation of ChimeraT induced a protective Th1-type immune response and thus could be considered in future studies as a vaccine candidate against human VL.

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Section: Discussionmentioning

confidence: 99%

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

et al. 2020

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“…BALB/c mice were chosen based on their distinctive IgG subtype response between Th1 and Th2 immunity. [33,80,81] When applying MN arrays, animals were anesthetized by intraperitoneal injection (31 G) with a ketamine (50 mg kg À1 ) and xylazine (10 mg kg À1 ) mix (both Troy Laboratories, Smithfield, Australia) and its action reversed with atipamezole (Antisedan; Pfizer, Australia) diluted 1:10 in phosphatebuffered solution (PBS) delivered at 1 mg kg À1 . For retro-orbital blood sampling, mice were anesthetized with inhalational of methoxyflurane (Ceva Delvet Pty Ltd., Australia).…”

Section: Methodsmentioning

confidence: 99%

An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses

Coffey

Burg

Rananakomol

et al. 2022

Advanced NanoBiomed Research

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Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion depth, delivery energy/velocity, MN shape, and density. However, these effects have not been systematically investigated. Herein, the effect of MN density on antibody responses to influenza vaccination is assessed, keeping all other variables constant. MN arrays are manufactured within the “high‐density range” from 5 k microneedles cm−2 (n cm−2) to the “ultrahigh” 30 k n cm−2. Prior to this study, the highest MN density used for vaccination is 20 k n cm−2. Thus, MN array vaccination is evaluated over an unprecedented range. Cell viability is assessed in the skin after application and antibody responses at days 21/63. It is demonstrated that increasing MN density from 5 to 30 k n cm−2 increases both epidermal cell death and anti‐influenza IgG1, without an increase in anti‐influenza IgG2a. This suggests that MN density has a direct adjuvant effect on immune responses through Th2‐mediated signalling—a response critical for human vaccination.

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“…Another recent example of extended release PLGA microparticles is the encapsulation of a Leishmania protein antigen NH36 for vaccination against the parasitic infection leishmaniasis (Wang et al, 2017). Vaccines require booster doses in order to elicit an effective humoral immune response, thus single administration depot formulations can obviate the need for repeat injections and increase patient compliance.…”

Section: Double Emulsionmentioning

confidence: 99%

Poly(lactic‐co‐glycolic acid) devices: Production and applications for sustained protein delivery

Lee

Pokorski

2018

WIREs Nanomed Nanobiotechnol

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Injectable or implantable poly(lactic-co-glycolic acid) (PLGA) devices for the sustained delivery of proteins have been widely studied and utilized to overcome the necessity of repeated administrations for therapeutic proteins due to poor pharmacokinetic profiles of macromolecular therapies. These devices can come in the form of microparticles, implants, or patches depending on the disease state and route of administration. Furthermore, the release rate can be tuned from weeks to months by controlling the polymer composition, geometry of the device, or introducing additives during device fabrication. Slow-release devices have become a very powerful tool for modern medicine. Production of these devices has initially focused on emulsion-based methods, relying on phase separation to encapsulate proteins within polymeric microparticles. Process parameters and the effect of additives have been thoroughly researched to ensure protein stability during device manufacturing and to control the release profile. Continuous fluidic production methods have also been utilized to create protein-laden PLGA devices through spray drying and electrospray production. Thermal processing of PLGA with solid proteins is an emerging production method that allows for continuous, high-throughput manufacturing of PLGA/protein devices. Overall, polymeric materials for protein delivery remain an emerging field of research for the creation of single administration treatments for a wide variety of disease. This review describes, in detail, methods to make PLGA devices, comparing traditional emulsion-based methods to emerging methods to fabricate protein-laden devices. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Peptide-Based Structures.

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3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

Cited by 9 publications

References 46 publications

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses

Poly(lactic‐co‐glycolic acid) devices: Production and applications for sustained protein delivery

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