Tetanus vaccination with a dissolving microneedle patch confers protective immune responses in pregnancy

Esser, E. Stein; Romanyuk, Andrey; Vassilieva, Elena V.; Jacob, Joshy; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna

doi:10.1016/j.jconrel.2016.06.026

Cited by 51 publications

(30 citation statements)

References 42 publications

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“…[46][47][48] In addition, the same research group used these microneedles made using polyvinyl alcohol and sucrose to successfully deliver tetanus, rabies and ebola vaccines along with synthetic vaccines made of layer-by-layer microparticles against respiratory syncytial virus. [49][50][51][52] On the other hand, Donnelly et al used "super swelling" microneedles made of hydrogel forming polymers (Gantrez S-97, polyethylene glycol and Na 2 CO 3 ) to deliver 0.32 g OVA across the skin of Sprague Dawley rats. [53] A peak plasma concentration of OVA was observed in 1 h that was sustained for another 5 h. These studies suggest that microneedles are one of the promising tools for enhancement of transdermal delivery for several types of macro molecules.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Banerjee

Ibsen

Iwao

et al. 2017

Adv Healthcare Materials

170

159

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Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg −1 insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes.

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Section: Discussionmentioning

confidence: 99%

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Banerjee

Ibsen

Iwao

et al. 2017

Adv Healthcare Materials

170

159

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“…Antibody titers were quantified with ELISA as described previously with biotinylated anti-IgG, IgG1, IgG2 antibodies (Southern Biotech, Birmingham, AL) against 100 ng/well monovalent H1N1 A/California/07/2009 subunit vaccine, A/Christchurch/16/2010 subunit vaccine, or recombinant HA A/California/07/2009 from BEI Resources (Manassas, VA) [42]. Hemagglutination inhibition (HAI) assays were performed according to the WHO laboratory diagnostics manual using washed turkey red blood cells [43].…”

Section: Methodsmentioning

confidence: 99%

“…IgG titers against chimeric HA proteins containing exotic HA head subtypes and commonly found seasonal HA stalks were measured to determine the antibody targets from H1N1 vaccinated mice; these chimeric proteins (cH6/1 and cH14/3) were created in a baculovirus system as described previously [44]. Influenza-specific antibody avidity was measured by ELISA in the presence of increasing concentrations (0–2.0 M) of the chaotropic agent guanidine thiocyanate (GTC) (Sigma), as previously described [42]. The avidity index was determined using Prism 7.03 Software (GraphPad, La Jolla, CA) by calculating the molar concentration of the chaotropic agent required to reduce the initial optical density by 50%.…”

Section: Methodsmentioning

confidence: 99%

Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza

Littauer

Mills

Brock

et al. 2018

Journal of Controlled Release

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The widely used influenza subunit vaccine would benefit from increased protection rates in vulnerable populations. Skin immunization by microneedle (MN) patch can increase vaccine immunogenicity, as well as increase vaccination coverage due to simplified administration. To further increase immunogenicity, we used granulocyte-macrophage colony stimulating factor (GM-CSF), an immunomodulatory cytokine already approved for skin cancer therapy and cancer support treatment. GM-CSF has been shown to be upregulated in skin following MN insertion. The GM-CSF-adjuvanted vaccine induced robust and long-lived antibody responses cross-reactive to homosubtypic and heterosubtypic influenza viruses. Addition of GM-CSF resulted in increased memory B cell persistence relative to groups given influenza vaccine alone and led to rapid lung viral clearance following lethal infection with homologous virus in the mouse model. Here we demonstrate that successful incorporation of the thermolabile cytokine GM-CSF into MN resulted in improved vaccine-induced protective immunity holding promise as a novel approach to improved influenza vaccination. To our knowledge, this is the first successful incorporation of a cytokine adjuvant into dissolvable MNs, thus advancing and diversifying the rapidly developing field of MN vaccination technology.

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“…In developed countries, it has been observed that tetanus infections occur in immunosuppressed patients, diabetics, the elderly who were not vaccinated in their childhood, and patients older than 50 years with serological tests with low levels of antibodies against tetanus toxin [167,168]. For this reason nowadays many efforts are focused on improving techniques for measuring antibodies against this toxin [169][170][171][172] and in the development tetanus neurotoxin neutralizing antibodies [171,173,174].…”

Section: Tetani Toxinsmentioning

confidence: 99%

Rapid Tests for Detection of Main Clostridial Toxins

Pérez-Etcheverry

Carmen

2017

IRA-JAS

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Tetanus vaccination with a dissolving microneedle patch confers protective immune responses in pregnancy

Cited by 51 publications

References 42 publications

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza

Rapid Tests for Detection of Main Clostridial Toxins

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