The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice
Background/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to dist...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/86 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587366290685952 |
|---|---|
| author | Eun Kim Muhammad S. Khan Juyeop Shin Shaohua Huang Alessandro Ferrari Donghoon Han Eunjin An Thomas W. Kenniston Irene Cassaniti Fausto Baldanti Dohyeon Jeong Andrea Gambotto |
| author_facet | Eun Kim Muhammad S. Khan Juyeop Shin Shaohua Huang Alessandro Ferrari Donghoon Han Eunjin An Thomas W. Kenniston Irene Cassaniti Fausto Baldanti Dohyeon Jeong Andrea Gambotto |
| author_sort | Eun Kim |
| collection | DOAJ |
| description | Background/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide. Methods: The rS1RS09 vaccine was administered via MAP or intramuscular injection in murine models. The immune responses of the MAP with and without gamma irradiation as terminal sterilization were assessed at doses of 5, 15, and 45 µg, alongside neutralizing antibody responses to Wuhan, Delta, and Omicron variants. The long-term storage stability was also evaluated through protein degradation analyses at varying temperatures. Results: The rS1RS09 vaccine elicited stronger immune responses and ACE2-binding inhibition than S1 monomer alone or trimer. The MAP delivery induced sgnificantly higher and longer-lasting S1-specific IgG responses for up to 70 weeks compared to intramuscular injections. Robust Th2-prevalent immune responses were generated in all the groups vaccinated via the MAP and significant neutralizing antibodies were elicited at 15 and 45 µg, showing dose-sparing potential. The rS1RS09 in MAP has remained stable with minimal protein degradation for 19 months at room temperature or under refrigeration, regardless of gamma-irradiation. After an additional month of storage at 42 °C, cit showed less than 3% degradation, ompared to over 23% in liquid vaccines Conclusions: Gamma-irradiated MAP-rS1RS09 is a promising platform for stable, scalable vaccine production and distribution, eliminating cold chain logistics. These findings support its potential for mass vaccination efforts, particularly in resource-limited settings. |
| format | Article |
| id | doaj-art-8451ddcad5ba47dc9d8549c9630c83da |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-8451ddcad5ba47dc9d8549c9630c83da2025-01-24T13:51:53ZengMDPI AGVaccines2076-393X2025-01-011318610.3390/vaccines13010086The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in MiceEun Kim0Muhammad S. Khan1Juyeop Shin2Shaohua Huang3Alessandro Ferrari4Donghoon Han5Eunjin An6Thomas W. Kenniston7Irene Cassaniti8Fausto Baldanti9Dohyeon Jeong10Andrea Gambotto11Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USAMedical Business Division, Raphas Co., Ltd., Seoul 07793, Republic of KoreaDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USAMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, 27100 Pavia, ItalyMedical Business Division, Raphas Co., Ltd., Seoul 07793, Republic of KoreaMedical Business Division, Raphas Co., Ltd., Seoul 07793, Republic of KoreaDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USAMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, 27100 Pavia, ItalyMolecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinico San Matteo, 27100 Pavia, ItalyMedical Business Division, Raphas Co., Ltd., Seoul 07793, Republic of KoreaDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USABackground/Objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide. Methods: The rS1RS09 vaccine was administered via MAP or intramuscular injection in murine models. The immune responses of the MAP with and without gamma irradiation as terminal sterilization were assessed at doses of 5, 15, and 45 µg, alongside neutralizing antibody responses to Wuhan, Delta, and Omicron variants. The long-term storage stability was also evaluated through protein degradation analyses at varying temperatures. Results: The rS1RS09 vaccine elicited stronger immune responses and ACE2-binding inhibition than S1 monomer alone or trimer. The MAP delivery induced sgnificantly higher and longer-lasting S1-specific IgG responses for up to 70 weeks compared to intramuscular injections. Robust Th2-prevalent immune responses were generated in all the groups vaccinated via the MAP and significant neutralizing antibodies were elicited at 15 and 45 µg, showing dose-sparing potential. The rS1RS09 in MAP has remained stable with minimal protein degradation for 19 months at room temperature or under refrigeration, regardless of gamma-irradiation. After an additional month of storage at 42 °C, cit showed less than 3% degradation, ompared to over 23% in liquid vaccines Conclusions: Gamma-irradiated MAP-rS1RS09 is a promising platform for stable, scalable vaccine production and distribution, eliminating cold chain logistics. These findings support its potential for mass vaccination efforts, particularly in resource-limited settings.https://www.mdpi.com/2076-393X/13/1/86COVID-19 vaccinemicroneedle array patchSARS-CoV-2S1 protein subunitgamma irradiation sterilizationthermostability |
| spellingShingle | Eun Kim Muhammad S. Khan Juyeop Shin Shaohua Huang Alessandro Ferrari Donghoon Han Eunjin An Thomas W. Kenniston Irene Cassaniti Fausto Baldanti Dohyeon Jeong Andrea Gambotto The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice Vaccines COVID-19 vaccine microneedle array patch SARS-CoV-2 S1 protein subunit gamma irradiation sterilization thermostability |
| title | The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice |
| title_full | The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice |
| title_fullStr | The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice |
| title_full_unstemmed | The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice |
| title_short | The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice |
| title_sort | long term immunity of a microneedle array patch of a sars cov 2 s1 protein subunit vaccine irradiated by gamma rays in mice |
| topic | COVID-19 vaccine microneedle array patch SARS-CoV-2 S1 protein subunit gamma irradiation sterilization thermostability |
| url | https://www.mdpi.com/2076-393X/13/1/86 |
| work_keys_str_mv | AT eunkim thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT muhammadskhan thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT juyeopshin thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT shaohuahuang thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT alessandroferrari thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT donghoonhan thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT eunjinan thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT thomaswkenniston thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT irenecassaniti thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT faustobaldanti thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT dohyeonjeong thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT andreagambotto thelongtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT eunkim longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT muhammadskhan longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT juyeopshin longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT shaohuahuang longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT alessandroferrari longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT donghoonhan longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT eunjinan longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT thomaswkenniston longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT irenecassaniti longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT faustobaldanti longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT dohyeonjeong longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice AT andreagambotto longtermimmunityofamicroneedlearraypatchofasarscov2s1proteinsubunitvaccineirradiatedbygammaraysinmice |