Dose sparing intradermal trivalent influenza (2010/2011) vaccination overcomes reduced immunogenicity of the 2009 H1N1 strain
State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region Vaccine
(Impact Factor: 3.62).
08/2012; 30(45):6427-35. DOI: 10.1016/j.vaccine.2012.08.014
We hypothesized that low dose intradermal vaccination of the trivalent influenza vaccine (TIV) delivered by the MicronJet600™ (NanoPass Technologies, Israel) would be non-inferior to the full dose intramuscular and mid dose Intanza(®) vaccination in the elderly and the chronically ill adults.
We performed a prospective randomized trial on elderly and chronically ill adults. Subjects were randomly assigned into 4 groups. Groups ID3 and ID9 received reduced dose ID TIV (3μg and 9μg of hemagglutinin (HA) per strain respectively) delivered by MicronJet600™ (NanoPass Technologies, Israel). Group INT9 received reduced dose ID TIV (9μg) delivered by Becton Dickinson's Soluvia™ device (Intanza(®)9, Sanofi-Pasteur, France). Control group IM15 received a full dose IM TIV (15μg). We measured antibody titers by hemagglutination inhibition (HAI) and microneutralization (MN) assays at baseline and day 21.
Baseline characteristics for all groups were similar (group and sample sizes: ID3=63; ID9=68; INT9=65; and IM15=66). At day 21 post vaccination, the GMT ratio and the seroconversion rates difference for all three strains of the ID vaccine groups were non-inferior to the IM vaccine group. The seroconversion rate, seroprotection rate, and the GMT of the H1N1 strains by HAI and MN assays were significantly higher in the ID groups compared with the full dose IM vaccine group. The seroconversion rates of the H3N2 strain by HAI assay were also significantly higher in the ID groups when compared with the full dose IM group. Direct comparison among the three ID groups showed no significant differences. No serious adverse events related to vaccination were reported.
Dose-sparing ID TIV can overcome reduced immunogenicity of the H1N1 strain, and according to some measures, for the H3N2 strain. At risk subjects indicated for the TIV should be considered for intradermal immunization to compensate for reduced immunogenicity.
Available from: Courtney Jarrahian
- "Intradermal delivery of influenza vaccine by microneedles can lead to longer-lasting and more-robust antibody responses than intramuscular vaccination in mice, suggesting the possibility of improved efficacy             . Clinical studies comparing intramuscular delivery of influenza vaccine to intradermal delivery in liquid form through hollow minineedles and microneedles have shown a superior immune response in the elderly when an equal dose is administered intradermally, and equivalent immune responses in younger adults with administration of a reduced dose       . With the emergence of microfabrication manufacturing technology over the past several decades, microneedles have been developed by academic laboratories and pharmaceutical companies . "
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ABSTRACT: Simple and efficacious delivery methods for influenza vaccines are needed to improve health outcomes and manage possible pandemics both in the United States and globally. One approach to meeting these needs is the microneedle patch (MNP), a small array of micron-scale needles that is applied to the skin like a bandage.
To inform additional technical developments and the eventual introduction of MNPs for influenza vaccination, we interviewed key opinion leaders in the United States for insights into the opportunities and challenges associated with this technology, particularly its potential for self-administration.
All interviewees expressed high support for administration of influenza vaccine in MNPs by health care providers and for self-administration in groups supervised by a provider. Self-administration via prescription and over-the-counter purchase of MNPs received lower levels of support. Interviewees also highlighted priorities that should be considered in the ongoing development of an influenza vaccine MNP, such as confirming it to be as efficacious as existing methods of influenza vaccine delivery and ensuring safety for self-administration. For patient and health care provider acceptability, important attributes are ease of use, short wear times, and an easily accessible application site.
Stakeholders agreed that using MNPs can help increase coverage, facilitate easy and safe delivery, reduce the cost of vaccination, and decrease the global morbidity and mortality associated with influenza. Another opportunity for this delivery method is the potential for self-administration. The prospect of reduced provider training requirements, increased thermostability, and high patient and provider acceptability makes it an attractive option for use in remote and low-resource settings worldwide. However, in addition to the technological challenges associated with producing the patch, developers must be mindful of cost considerations and key product attributes or requirements, such as usability, wear time, and proper disposal, that can affect how the product will be received in the marketplace.
Copyright © 2015. Published by Elsevier Ltd.
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ABSTRACT: Microelectromechanical systems (MEMS) are playing a prominent role in the development of many new and innovative biomedical devices, but they remain a relatively underused technology in nephrology. The future landscape of clinical medicine and research will only see further expansion of MEMS-based technologies in device designs and applications. This enthusiasm stems from the ability to create small-scale device features with high precision in a cost-effective manner. MEMS also offers the possibility to integrate multiple components into a single device. The adoption of MEMS has the potential to revolutionize how nephrologists manage kidney disease by improving the delivery of renal replacement therapies and enhancing the monitoring of physiologic parameters. To introduce nephrologists to MEMS, this review will first define relevant terms and describe the basic processes used to fabricate devices. Next, a survey of MEMS devices being developed for various biomedical applications will be illustrated with current examples. Finally, MEMS technology specific to nephrology will be highlighted and future applications will be examined. The adoption of MEMS offers novel avenues to improve the care of kidney disease patients and assist nephrologists in clinical practice. This review will serve as an introduction for nephrologists to the exciting world of MEMS.
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ABSTRACT: Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.
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