نبذة مختصرة : Background: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza.
Methodology: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717.
Findings: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 μg group and 1 participant withdrew from the 7.5 μg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 μg and 7.5 μg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 μg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180.
Conclusions: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.
Competing Interests: Jon Kluge, Jonathan L. Portman, Anna Markowska and Lynda Tussey are employees of the clinical trial sponsor Vaxess Technologies. Naveen Garg, Guy Tellier and Noah Vale are employees of Centricity Research, the clinical research organization responsible for conducting the VX103-01 clinical trial. All Vaxess related patent information is included below. These competing interests do not impact the authors adherence to PLOS ONE policies and data sharing. Country Application No. Publication No Application Title US 17/714025 US-2022-0339416-A1 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF WO PCT/US2020/055139 WO 2021/072313 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF AU 2020364146 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF CA 3156676 3156676 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF CN 202080071018.4 114728154 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF EP 20874211.4 4041330 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF JP 2022-521636 2022-551910 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF KR 10-2022-7014919 10-2022-0093120 SILK FIBROIN-BASED MICRONEEDLES AND USES THEREOF US 17/958148 US-2023-0190911-A1 VACCINE FORMULATIONS WITH INCREASED STABILITY WO PCT/US2017/052301 WO 2018/053524 VACCINE FORMULATIONS WITH INCREASED STABILITY AU 2017327009 2017327009 VACCINE FORMULATIONS WITH INCREASED STABILITY CA 3037337 3037337 VACCINE FORMULATIONS WITH INCREASED STABILITY EP 17778047.5 3532093 VACCINE FORMULATIONS WITH INCREASED STABILITY US 17/157451 US-2021-0283597-A1 POLYMER-BASED BIOSPECIMEN COLLECTION DEVICES AND USES THEREOF WO PCT/US2019/043727 WO 2020/023906 POLYMER-BASED BIOSPECIMEN COLLECTION DEVICES AND USES THEREOF EP 19761984.4 3830576 POLYMER-BASED BIOSPECIMEN COLLECTION DEVICES AND USES THEREOF US 17/044439 US-2021-0085598-A1 MICRONEEDLE COMPRISING SILK FIBROIN APPLIED TO A DISSOLVABLE BASE WO PCT/US2019/025467 WO 2019/195350 MICRONEEDLE COMPRISING SILK FIBROIN APPLIED TO A DISSOLVABLE BASE AU 2019247655 MICRONEEDLE COMPRISING SILK FIBROIN APPLIED TO A DISSOLVABLE BASE CA 3096036 3096036 MICRONEEDLE COMPRISING SILK FIBROIN APPLIED TO A DISSOLVABLE BASE EP 19718034.2 3773477 MICRONEEDLE COMPRISING SILK FIBROIN APPLIED TO A DISSOLVABLE BASE WO PCT/US2023/026036 WO 2023/250117 APPLICATOR FOR MEDICAMENT PATCH US 17/991525 US-2023-0270842-A1 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF WO PCT/US2021/033776 WO 2021/237174 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF AU 2021276000 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF CA 3183930 3183930 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF CN 202180061194.4 CN116406285A COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF EP 21809075.1 4153139 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF JP 2022-571231 2023-527175 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF KR 10-2022-7044731 COMPOSITIONS AND DEVICES FOR VACCINE RELEASE AND USES THEREOF US 18/563337 MICRONEEDLE VACCINE AGAINST SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2)
(Copyright: © 2024 Garg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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