A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; Damme, Pierre Van

doi:10.1016/j.vaccine.2016.09.008

Cited by 39 publications

(42 citation statements)

References 41 publications

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“…MPLA (Monophosphoryl Lipid A) is a potent activator of TLR4 that boosts a combined Th1/Th2 response [52]. AddaVax is a squalene-based oil-in-water nano-emulsion adjuvant similar to MF59 that has been licensed in Europe for flu vaccines with the ability to induce a balanced Th1/Th2-type response [53, 54]. Our studies revealed that mice immunized with 25 μg of rAs16 formulated with Alhydrogel produced a similar level of lung larva reduction (38.9%) as observed with 50 μg of rAs16 formulated with ISA720 (36.7%); accompanied by high levels of IgG1 and IL-5, but without IFN-γ or TNF-α production.…”

Section: Discussionmentioning

confidence: 99%

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

et al. 2017

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BackgroundAscariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood.Methodology/Principal findingsAs16 and As14 were highly expressed as soluble recombinant proteins (rAs16 and rAs14) in Pichia pastoris. The yeast-expressed rAs16 was highly recognized by immune sera from mice infected with A. suum eggs and elicited 99.6% protection against A. suum re-infection. Mice immunized with rAs16 formulated with ISA720 displayed significant larva reduction (36.7%) and stunted larval development against A. suum eggs challenge. The protective immunity was associated with a predominant Th2-type response characterized by high titers of serological IgG1 (IgG1/IgG2a > 2000) and high levels of IL-4 and IL-5 produced by restimulated splenocytes. A similar level of protection was observed in mice immunized with rAs16 formulated with alum (Alhydrogel), known to induce mainly a Th2-type immune response, whereas mice immunized with rAs16 formulated with MPLA or AddaVax, both known to induce a Th1-type biased response, were not significantly protected against A. suum infection. The rAs14 protein was not recognized by A. suum infected mouse sera and mice immunized with rAs14 formulated with ISA720 did not show significant protection against challenge infection, possibly due to the protein’s inaccessibility to the host immune system or a Th1-type response was induced which would counter a protective Th2-type response.Conclusions/SignificanceYeast-expressed rAs16 formulated with ISA720 or alum induced significant protection in mice against A. suum egg challenge that associates with a Th2-skewed immune response, suggesting that rAS16 could be a feasible vaccine candidate against ascariasis.

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Section: Discussionmentioning

confidence: 99%

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

et al. 2017

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“…In order to promote a regulatory response to the PIC19-A3 autoantigen we employed the CE-marked MJ600 device to target skin DCs whilst minimising the trauma of intradermal delivery and any ensuing cutaneous inflammation (Mutyambizi et al, 2009). The device has three hollow silicon MNs of 600μm length and has been used extensively in clinical studies to deliver a range of macromolecular formulations including insulin (Kochba et al, 2016), varicella zoster (Beals et al, 2016), polio (Anand et al, 2015;Troy et al, 2015) and seasonal and pandemic influenza vaccines (Della Cioppa et al, 2014;Hung et al, 2012a;Hung et al, 2012b;Levin et al, 2014;Levin et al, 2016;Van Damme et al, 2009). However, whilst there are a number of publications showing successful therapeutic readouts upon use of hollow MNs, there is a paucity of information related to the behaviour of injected materials in the local environment and how formulation or physicochemical drug properties influence distribution and retention in situ (Mansoor et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy

Dul

Nikolić

Stefanidou

et al. 2019

International Journal of Pharmaceutics

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Antigen specific immunotherapy aims to tolerise patients to specific autoantigens that are responsible for the pathology of an autoimmune disease. Immune tolerance is generated in conditions where the immune response is supressed and thus gold nanoparticles (AuNPs) are an attractive drug delivery platform due to their anti-inflammatory effects and their potential to facilitate temporal and spatial delivery of a peptide autoantigen in conjunction with pro-tolerogenic elements. In this study we have covalently attached an autoantigen, currently under clinical evaluation for the treatment of type 1 diabetes (PIC19-A3 peptide), to AuNPs to create nanoscale (<5nm), negatively charged (-40 to-60mV) AuNP-peptide complexes for immunotherapy. We also employ a clinically approved microneedle delivery system, MicronJet600, to facilitate minimally-invasive intradermal delivery of the nanoparticle constructs to target skin-resident antigen presenting cells, which are known to be apposite target cells for immunotherapy. The AuNP-peptide complexes remain physically stable upon extrusion through microneedles and when delivered into ex vivo human skin they are able to diffuse rapidly and widely throughout the dermis (their site of deposition) and, perhaps more surprisingly, the overlying epidermal layer. Intracellular uptake was extensive, with Langerhans cells proving to be the most efficient cells at internalising the AuNP-peptide complex (94% of the local population within the treated region of skin). In vitro studies showed that uptake of the AuNP-peptide complexes by dendritic cells reduced the capacity of these cells to activate naïve T cells. This indicator of biological functionality encourages further development of the AuNP-peptide formulation, which is now being evaluated in clinical trials.

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“…The World Health officials are aiming to eliminate measles and such a microneedle patch can be the game changer [12]. Study by Levin et al and Behrens et al confirmed the immunogenicity and safety of intradermal delivery of virosomal influenza vaccine and vaccine containing heat-labile toxin from Escherichia coli against travellers' diarrhea respectively in humans [42,43].…”

Section: Transdermal Routementioning

confidence: 99%

Advances Towards Painless Vaccination and Newer Modes of Vaccine Delivery

Garg

Aggarwal

2017

Indian J Pediatr

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Vaccines have been successful in reducing the mortality and morbidity, but most of them are delivered by intramuscular or intravenous route. They are associated with pain to the baby and bring lot of anxiety for the parents. There has been a marked increase in the number of injections required in first two years of life for completing the vaccination schedule. Hence, there is a need to have a painless vaccine delivery system. Numerous new routes of vaccination like, oral, nasal and transdermal routes are being tried. Oral polio and intranasal influenza have already been a success. Other newer approaches like edible vaccines, nasal sprays, dry powder preparations, jet injectors, microneedles and nanopatches are promising in delivering painless vaccines. Many of them are under clinical trials. These vaccine delivery systems will not only be painless but also cost effective, safe and easy to administer in mass population. They may be devoid of the need of cold chain. Painless delivery system will ensure better compliance to vaccination schedule.

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A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly

Cited by 39 publications

References 41 publications

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy

Advances Towards Painless Vaccination and Newer Modes of Vaccine Delivery

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