Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague
Abstract Yersinia pestis, the causative agent of plague, remains a significant global health hazard and a potential top‐tier biothreat despite modern medical advances. Here, two mRNA constructs encoding different versions of the low‐calcium response virulence (LcrV) protective antigen, an essential...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202501286 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849405076495400960 |
|---|---|
| author | Uri Elia Yinon Levy Hila Cohen Ayelet Zauberman David Gur Inbal Hazan‐Halevy Moshe Aftalion Shani Benarroch Erez Bar‐Haim Orit Redy‐Keisar Ofer Cohen Dan Peer Emanuelle Mamroud |
| author_facet | Uri Elia Yinon Levy Hila Cohen Ayelet Zauberman David Gur Inbal Hazan‐Halevy Moshe Aftalion Shani Benarroch Erez Bar‐Haim Orit Redy‐Keisar Ofer Cohen Dan Peer Emanuelle Mamroud |
| author_sort | Uri Elia |
| collection | DOAJ |
| description | Abstract Yersinia pestis, the causative agent of plague, remains a significant global health hazard and a potential top‐tier biothreat despite modern medical advances. Here, two mRNA constructs encoding different versions of the low‐calcium response virulence (LcrV) protective antigen, an essential virulence factor of Y. pestis, are designed and evaluated. Next, the immunogenicity and protective efficacy both independently and in combination is assessed with the previously reported F1‐encoding mRNA construct in the well‐established mouse model of pneumonic plague. The findings reveal that human Fc‐conjugated F1 + LcrV combination mRNA vaccination resulted in significant immune activation and substantial protection against intranasal Y. pestis challenge. Notably, the combined vaccine demonstrates protective efficacy against two highly virulent wild‐type Y. pestis strains representing distinct biovars and an atypical, unencapsulated strain. This study represents the first comprehensive evaluation of mRNA constructs encoding innovatively designed versions of LcrV and F1 for pneumonic plague prevention, addressing critical gaps in current vaccination approaches. This study establishes the mRNA‐lipid nanoparticle (LNP) platform as a promising tool for addressing bacterial pathogens, including those resistant to antibiotics. By broadening its applicability to diverse threats, this technology represents an innovative approach to tackling some of the most pressing challenges in global health. |
| format | Article |
| id | doaj-art-9d60a0feb9984758bc6b290519239147 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9d60a0feb9984758bc6b2905192391472025-08-20T03:36:45ZengWileyAdvanced Science2198-38442025-07-011226n/an/a10.1002/advs.202501286Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic PlagueUri Elia0Yinon Levy1Hila Cohen2Ayelet Zauberman3David Gur4Inbal Hazan‐Halevy5Moshe Aftalion6Shani Benarroch7Erez Bar‐Haim8Orit Redy‐Keisar9Ofer Cohen10Dan Peer11Emanuelle Mamroud12Department of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelLaboratory of Precision NanoMedicine Shmunis School for Biomedicine and Cancer Research George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv 69978 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelLaboratory of Precision NanoMedicine Shmunis School for Biomedicine and Cancer Research George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv 69978 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Organic Chemistry Israel Institute for Biological Research Ness‐Ziona 76100 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelLaboratory of Precision NanoMedicine Shmunis School for Biomedicine and Cancer Research George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv 69978 IsraelDepartment of Biochemistry and Molecular Genetics Israel Institute for Biological Research Ness‐Ziona 76100 IsraelAbstract Yersinia pestis, the causative agent of plague, remains a significant global health hazard and a potential top‐tier biothreat despite modern medical advances. Here, two mRNA constructs encoding different versions of the low‐calcium response virulence (LcrV) protective antigen, an essential virulence factor of Y. pestis, are designed and evaluated. Next, the immunogenicity and protective efficacy both independently and in combination is assessed with the previously reported F1‐encoding mRNA construct in the well‐established mouse model of pneumonic plague. The findings reveal that human Fc‐conjugated F1 + LcrV combination mRNA vaccination resulted in significant immune activation and substantial protection against intranasal Y. pestis challenge. Notably, the combined vaccine demonstrates protective efficacy against two highly virulent wild‐type Y. pestis strains representing distinct biovars and an atypical, unencapsulated strain. This study represents the first comprehensive evaluation of mRNA constructs encoding innovatively designed versions of LcrV and F1 for pneumonic plague prevention, addressing critical gaps in current vaccination approaches. This study establishes the mRNA‐lipid nanoparticle (LNP) platform as a promising tool for addressing bacterial pathogens, including those resistant to antibiotics. By broadening its applicability to diverse threats, this technology represents an innovative approach to tackling some of the most pressing challenges in global health.https://doi.org/10.1002/advs.202501286lipid nanoparticlesmRNAvaccineY. pestis |
| spellingShingle | Uri Elia Yinon Levy Hila Cohen Ayelet Zauberman David Gur Inbal Hazan‐Halevy Moshe Aftalion Shani Benarroch Erez Bar‐Haim Orit Redy‐Keisar Ofer Cohen Dan Peer Emanuelle Mamroud Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague Advanced Science lipid nanoparticles mRNA vaccine Y. pestis |
| title | Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague |
| title_full | Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague |
| title_fullStr | Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague |
| title_full_unstemmed | Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague |
| title_short | Novel Bivalent mRNA‐LNP Vaccine for Highly Effective Protection against Pneumonic Plague |
| title_sort | novel bivalent mrna lnp vaccine for highly effective protection against pneumonic plague |
| topic | lipid nanoparticles mRNA vaccine Y. pestis |
| url | https://doi.org/10.1002/advs.202501286 |
| work_keys_str_mv | AT urielia novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT yinonlevy novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT hilacohen novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT ayeletzauberman novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT davidgur novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT inbalhazanhalevy novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT mosheaftalion novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT shanibenarroch novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT erezbarhaim novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT oritredykeisar novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT ofercohen novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT danpeer novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague AT emanuellemamroud novelbivalentmrnalnpvaccineforhighlyeffectiveprotectionagainstpneumonicplague |