Acceptability of an inactivated influenza vaccine delivered by microneedle patch: Results from a phase I clinical trial of safety, reactogenicity, and immunogenicity

Frew, Paula M.; Paine, Michele; Rouphael, Nadine; Schamel, Jay; Chung, Yunmi; Mulligan, Mark J.; Prausnitz, Mark R.

doi:10.1016/j.vaccine.2020.07.064

Cited by 50 publications

(49 citation statements)

References 19 publications

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“…7 Four clinical trials of influenza vaccination have used dissolving patches. 5,[8][9][10] The TIVMNP2015 study showed that a microneedle patch containing an influenza vaccine is equivalent in safety and efficacy to intramuscular injection. 5 This effective immunological response can lead to a dosesparing effect, wherein the same immunological response can be triggered by a reduced antigen dose.…”

Section: Introductionmentioning

confidence: 99%

Safety and dose-sparing effect of Japanese encephalitis vaccine administered by microneedle patch in uninfected, healthy adults (MNA-J): a randomised, partly blinded, active-controlled, phase 1 trial

et al. 2022

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Background It is unclear whether microneedle vaccinations of Japanese encephalitis virus can induce sufficient neutralising antibodies and reduce the amount of vaccine needed. We aimed to assess the safety and dose-sparing effect of a microneedle vaccine patch against Japanese encephalitis in healthy individuals who are naive to both the vaccine and natural infection. MethodsThe MNA-J study was a randomised, partly blinded, active-controlled, phase 1 clinical trial at Hokkaido University (Sapporo, Japan) that enrolled healthy adults aged 20-34 years with no history of Japanese encephalitis vaccination nor of infection as confirmed by seronegativity. We excluded individuals who had been infected with or vaccinated against Japanese encephalitis. Eligible participants were randomly assigned (1:1:1) to one of three groups to receive inactivated Japanese encephalitis vaccine administered twice, 3 weeks apart, by either 2•5 μg per injection by subcutaneous injection, 0•63 μg per patch by high-dose microneedle array (MNA-25%), or 0•25 μg per patch by low-dose microneedle array (MNA-10%). The randomisation sequence, using stratification by cohort and blocks of six, was computer-generated by a statistician who was unaware of group assignment. After administration, the remaining amount of unadministered vaccine was measured by ELISA and calculated as the delivered amount of vaccine. The primary outcome was the neutralising antibody titre at day 42 after first immunisation. Successful seroconversion was defined as post-vaccination titres of 1•3 (log 10 ) or higher in individuals whose pre-vaccination titres had been less than 1 (log 10 ). This study is registered with the Japan Registry of Clinical Trials (s011190004). FindingsBetween Aug 31 and Sept 2, 2019, 39 participants were enrolled and each was randomly assigned to a group (n=13 per group). No serious adverse events were observed. All participants in the microneedle array groups had a localised erythematous reaction. The amount of vaccine delivered by microneedle array to each participant was 0•63-1•15 μg (50-92%) of the full 1•26 μg for the MNA-25% group and 0•25-0•41 μg (51-84%) of the full 0•50 μg for the MNA-10% group. All participants demonstrated seroconversion at day 42, and the mean titres (log 10 ) were 2•55 for MNA-25%, 2•04 for MNA-10%, and 2•08 for subcutaneous injection.Interpretation A microneedle patch of the Japanese encephalitis vaccine is safe, well tolerated, and immunogenically effective. The dose-sparing effect suggests a significant potential to reduce the amount of immunogens needed. However, improved delivery is needed to make it more tolerable and user friendly.Funding FUJIFILM.

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Section: Introductionmentioning

confidence: 99%

Safety and dose-sparing effect of Japanese encephalitis vaccine administered by microneedle patch in uninfected, healthy adults (MNA-J): a randomised, partly blinded, active-controlled, phase 1 trial

et al. 2022

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“…Numerous studies have shown that adults, children, parents, and clinicians prefer MN patch delivery over hypodermic injection. 35 , 36 , 37 , 38 When human subjects experienced both MN patch application to the skin and iontophoretic sweat testing in a prior study, there was no significant difference in reported pain between the two procedures. 27 Placebo MN patches, as well as MN patches administering various drugs and vaccines, have been shown to be well tolerated, with only transient, mild erythema reported as the most common side effect.…”

Section: Resultsmentioning

confidence: 98%

“…The fact that MN patches are generally perceived as painless 20,34,35 may also make this method of pilocarpine delivery more attractive to healthcare providers, patients, and their caregivers. Numerous studies have shown that adults, children, parents, and clinicians prefer MN patch delivery over hypodermic injection 35‐38 . When human subjects experienced both MN patch application to the skin and iontophoretic sweat testing in a prior study, there was no significant difference in reported pain between the two procedures 27 .…”

Section: Resultsmentioning

confidence: 99%

Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing

Hart

Norton

et al. 2021

Bioengineering & Transla Med

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The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine‐loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 μm long that were made of water‐soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm2 pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more‐accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.

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“…[ 34 ] Ever since, the field of microneedle‐based transdermal drug delivery has experienced a rapid expansion for administering a wide variety of drugs, vaccines, or even genes. [ 35–43 ] Several of these microneedle delivery devices have been FDA‐approved or are currently in the clinical evaluation stage.…”

Section: Historical Evolution Of Microneedle‐based Sensorsmentioning

confidence: 99%

Lab under the Skin: Microneedle Based Wearable Devices

Teymourian

Tehrani

Mahato

et al. 2021

Adv Healthcare Materials

206

140

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While the current smartwatches and cellphones can readily track mobility and vital signs, a new generation of wearable devices is rapidly developing to enable users to monitor their health parameters at the molecular level. Within this emerging class of wearables, microneedle‐based transdermal sensors are in a prime position to play a key role in synergizing the significant advantages of dermal interstitial fluid (ISF) as a rich source of clinical indicators and painless skin pricking to allow the collection of real‐time diagnostic information. While initial efforts of microneedle sensing focused on ISF extraction coupled with either on‐chip analysis or off‐chip instrumentation, the latest trend has been oriented toward assembling electrochemical biosensors on the tip of microneedles to allow direct continuous chemical measurements. In this context, significant advances have recently been made in exploiting microneedle‐based devices for real‐time monitoring of various metabolites, electrolytes, and therapeutics and toward the simultaneous multiplexed detection of key chemical markers; yet, there are several grand challenges that still exist. In this review, we outline current progress, recent trends, and new capabilities of microneedle‐empowered sensors, along with the current unmet challenges and a future roadmap toward transforming the latest innovations in the field to commercial products.

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Acceptability of an inactivated influenza vaccine delivered by microneedle patch: Results from a phase I clinical trial of safety, reactogenicity, and immunogenicity

Cited by 50 publications

References 19 publications

Safety and dose-sparing effect of Japanese encephalitis vaccine administered by microneedle patch in uninfected, healthy adults (MNA-J): a randomised, partly blinded, active-controlled, phase 1 trial

Safety and dose-sparing effect of Japanese encephalitis vaccine administered by microneedle patch in uninfected, healthy adults (MNA-J): a randomised, partly blinded, active-controlled, phase 1 trial

Administration of pilocarpine by microneedle patch as a novel method for cystic fibrosis sweat testing

Lab under the Skin: Microneedle Based Wearable Devices

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