Dose sparing intradermal trivalent influenza (2010/2011) vaccination overcomes reduced immunogenicity of the 2009 H1N1 strain
ABSTRACT 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.
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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.Advances in chronic kidney disease 11/2013; 20(6):516-35. DOI:10.1053/j.ackd.2013.08.006 · 1.94 Impact Factor
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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.The Journal of Immunology 01/2014; 192(4). DOI:10.4049/jimmunol.1302743 · 5.36 Impact Factor
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ABSTRACT: Vaccines have to be administered via an appropriate route, i.e. a route, which is optimal regarding safety, immunogenicity and practicability. In addition, there are factors, such as body site, needle length, injection technique, depth of injection, type of antigen, vaccine formulation, adjuvants, age, sex, race/ethnicity, body mass, and pre-existing immunity, which can have an impact on the reactogenicity and tolerability and/or on the immunogenicity of a given vaccine. For parenteral vaccine administration there are currently three routes licensed: intramuscular, subcutaneous and intradermal, either by using conventional hypodermic needles or by using alternative or needle-free injection devices. The factors potentially impacting on the 'performance' of a given route of administration, as reported in recent literature, are outlined and discussed in view of their importance. These factors need to be accounted and controlled for when designing vaccine studies and should be reported in a transparent and standardised way in publications.Expert Review of Vaccines 02/2014; DOI:10.1586/14760584.2014.883285 · 4.22 Impact Factor