Thermostability of Measles and Rubella Vaccines in a Microneedle Patch

Joyce, Jessica C.; Collins, Marcus L.; Rota, Paul A.; Prausnitz, Mark R.

doi:10.1002/adtp.202100095

Cited by 7 publications

(5 citation statements)

References 53 publications

(68 reference statements)

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“…[25,228,229] Other strategies include using a volatile organic solvent, such as chloroform, during the MNA casting process [230] or altering the pH and buffer composition of the solvent used while drying measles-or rubellacontaining films to significantly different viral titers. [231] Interestingly, the pH and buffer that yielded the highest viral titer of Measles were different than the combination that yielded the highest titer of Rubella, indicating that manufacturing parameters must be tuned to the specific vaccine or immunotherapy being delivered. Future work will be required to reveal additional manufacturing parameters critical to the stability of the vaccine within the MNA, and how both manufacturing and formulation strategies can be optimized to best maintain the antigenicity of vaccines and immunotherapies delivered via MNAs.…”

Section: Manufacturing Condition Modifications To Maintain Immunogeni...mentioning

confidence: 99%

Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses—often more protective or therapeutic—compared to conventional needle delivery. MNAs also offer logistical benefits, such as self‐administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here we discuss the unique advantages of MNA, as well as critical challenges – such as manufacturing and sterility issues – the field faces to enable widespread deployment. We explain how MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies. We also discuss specific strategies to reduce off‐target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. We then examine clinical research using MNAs. We conclude with drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use.This article is protected by copyright. All rights reserved

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Section: Manufacturing Condition Modifications To Maintain Immunogeni...mentioning

confidence: 99%

Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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“…Data are now being generated, including in this trial, to support this expectation. MR vaccines have been shown to have improved thermostability on other MAP formats compared with the standard, lyophilized presentation [25]. The controlled temperature excursion data presented here suggest that MR HD-MAPs will be suitable for use in the controlled temperature chain (CTC), facilitating their use in outreach settings.…”

Section: Discussionmentioning

confidence: 89%

Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial

Baker,

Bermingham,

Leelasena

et al. 2023

Vaccines

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Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID50] measles, ~4300 CCID50 rubella); high-dose MR-HD-MAPs (~9300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8 °C for at least 24 months. When MR HD-MAPs stored at 2–8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

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“…Data are now being generated, including in this trial, to support this expectation. MR vaccines have been shown to have improved thermostability on other MAP formats compared with the standard, lyophilized presentation [23]. The controlled temperature excursion data presented here suggest that MR HD-MAPs will be suitable for use in the controlled temperature chain (CTC), facilitating their use in outreach settings.…”

Section: Discussionmentioning

confidence: 89%

Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial

Baker,

Bermingham,

Leelasena

et al. 2023

Preprint

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Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

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Thermostability of Measles and Rubella Vaccines in a Microneedle Patch

Cited by 7 publications

References 53 publications

Exploiting Unique Features of Microneedles to Modulate Immunity

Exploiting Unique Features of Microneedles to Modulate Immunity

Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial

Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial

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