Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy
Abstract The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, str...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202404159 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850201513097428992 |
|---|---|
| author | Rita C. Acúrcio Ron Kleiner Daniella Vaskovich‐Koubi Bárbara Carreira Yulia Liubomirski Carolina Palma Adva Yeheskel Eilam Yeini Ana S. Viana Vera Ferreira Carlos Araújo Michael Mor Natalia T. Freund Eran Bacharach João Gonçalves Mira Toister‐Achituv Manon Fabregue Solene Matthieu Capucine Guerry Ana Zarubica Sarit Aviel‐Ronen Helena F. Florindo Ronit Satchi‐Fainaro |
| author_facet | Rita C. Acúrcio Ron Kleiner Daniella Vaskovich‐Koubi Bárbara Carreira Yulia Liubomirski Carolina Palma Adva Yeheskel Eilam Yeini Ana S. Viana Vera Ferreira Carlos Araújo Michael Mor Natalia T. Freund Eran Bacharach João Gonçalves Mira Toister‐Achituv Manon Fabregue Solene Matthieu Capucine Guerry Ana Zarubica Sarit Aviel‐Ronen Helena F. Florindo Ronit Satchi‐Fainaro |
| author_sort | Rita C. Acúrcio |
| collection | DOAJ |
| description | Abstract The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next‐generation multiepitope nanovaccines co‐deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD‐L1 expression. As a case study, we focused on SARS‐CoV‐2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular‐ and humoral‐specific responses against SARS‐CoV‐2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS‐CoV‐2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology‐based vaccines, it is shown that the lyophilized nanovaccine is stable for long‐term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats. |
| format | Article |
| id | doaj-art-b5734eacdf3b49c7be9c99d042cb5913 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b5734eacdf3b49c7be9c99d042cb59132025-08-20T02:11:59ZengWileyAdvanced Science2198-38442024-10-011140n/an/a10.1002/advs.202404159Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 ImmunotherapyRita C. Acúrcio0Ron Kleiner1Daniella Vaskovich‐Koubi2Bárbara Carreira3Yulia Liubomirski4Carolina Palma5Adva Yeheskel6Eilam Yeini7Ana S. Viana8Vera Ferreira9Carlos Araújo10Michael Mor11Natalia T. Freund12Eran Bacharach13João Gonçalves14Mira Toister‐Achituv15Manon Fabregue16Solene Matthieu17Capucine Guerry18Ana Zarubica19Sarit Aviel‐Ronen20Helena F. Florindo21Ronit Satchi‐Fainaro22Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalDepartment of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelDepartment of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalDepartment of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalThe Blavatnik Center for Drug Discovery Tel Aviv University Tel Aviv 6997801 IsraelDepartment of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelCenter of Chemistry and Biochemistry Faculty of Sciences University of Lisbon Lisbon 1749‐016 PortugalResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalDepartment of Clinical Microbiology and Immunology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelDepartment of Clinical Microbiology and Immunology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelThe Shmunis School of Biomedicine and Cancer Research George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv 6997801 IsraelResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalInter‐Lab, a subsidiary of Merck KGaA, South Industrial Area Yavne 8122004 IsraelCentre d'Immunophénomique Aix Marseille Université Inserm, CNRS, PHENOMIN Marseille 13284 FranceCentre d'Immunophénomique Aix Marseille Université Inserm, CNRS, PHENOMIN Marseille 13284 FranceCentre d'Immunophénomique Aix Marseille Université Inserm, CNRS, PHENOMIN Marseille 13284 FranceCentre d'Immunophénomique Aix Marseille Université Inserm, CNRS, PHENOMIN Marseille 13284 FranceAdelson School of Medicine Ariel University Ariel 4070000 IsraelResearch Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Lisbon 1649‐003 PortugalDepartment of Physiology and Pharmacology Faculty of Medicine Tel Aviv University Tel Aviv 6997801 IsraelAbstract The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next‐generation multiepitope nanovaccines co‐deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD‐L1 expression. As a case study, we focused on SARS‐CoV‐2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular‐ and humoral‐specific responses against SARS‐CoV‐2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS‐CoV‐2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology‐based vaccines, it is shown that the lyophilized nanovaccine is stable for long‐term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.https://doi.org/10.1002/advs.202404159Dendritic cellsIntranasalMHC class I and MHC class II peptidesNanovaccinesPD‐1/PD‐L1 immune checkpointsSARS‐CoV‐2 |
| spellingShingle | Rita C. Acúrcio Ron Kleiner Daniella Vaskovich‐Koubi Bárbara Carreira Yulia Liubomirski Carolina Palma Adva Yeheskel Eilam Yeini Ana S. Viana Vera Ferreira Carlos Araújo Michael Mor Natalia T. Freund Eran Bacharach João Gonçalves Mira Toister‐Achituv Manon Fabregue Solene Matthieu Capucine Guerry Ana Zarubica Sarit Aviel‐Ronen Helena F. Florindo Ronit Satchi‐Fainaro Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy Advanced Science Dendritic cells Intranasal MHC class I and MHC class II peptides Nanovaccines PD‐1/PD‐L1 immune checkpoints SARS‐CoV‐2 |
| title | Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy |
| title_full | Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy |
| title_fullStr | Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy |
| title_full_unstemmed | Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy |
| title_short | Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy |
| title_sort | intranasal multiepitope pd l1 sirna based nanovaccine the next gen covid 19 immunotherapy |
| topic | Dendritic cells Intranasal MHC class I and MHC class II peptides Nanovaccines PD‐1/PD‐L1 immune checkpoints SARS‐CoV‐2 |
| url | https://doi.org/10.1002/advs.202404159 |
| work_keys_str_mv | AT ritacacurcio intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT ronkleiner intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT daniellavaskovichkoubi intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT barbaracarreira intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT yulialiubomirski intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT carolinapalma intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT advayeheskel intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT eilamyeini intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT anasviana intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT veraferreira intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT carlosaraujo intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT michaelmor intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT nataliatfreund intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT eranbacharach intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT joaogoncalves intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT miratoisterachituv intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT manonfabregue intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT solenematthieu intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT capucineguerry intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT anazarubica intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT saritavielronen intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT helenafflorindo intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy AT ronitsatchifainaro intranasalmultiepitopepdl1sirnabasednanovaccinethenextgencovid19immunotherapy |