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Published on: August 21, 2019
A single-dose F1-based mRNA-LNP vaccine provides protection against the lethal plague bacterium
Edo Kon1,2,3,4, Yinon Levy5, Uri Elia1,2,3,4,5
1Laboratory of Precision NanoMedicine, Shmunis School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Abstract:
Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data concerning the platform's effectiveness against bacterial pathogens are limited. Here, we developed an effective mRNA-LNP vaccine against a lethal bacterial pathogen by optimizing mRNA payload guanine and cytosine content and antigen design. We designed a nucleoside-modified mRNA-LNP vaccine based on the bacterial F1 capsule antigen, a major protective component of Yersinia pestis, the etiological agent of plague. Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of humankind. Now, the disease is treated effectively with antibiotics; however, in the case of a multiple-antibiotic-resistant strain outbreak, alternative countermeasures are required. Our mRNA-LNP vaccine elicited humoral and cellular immunological responses in C57BL/6 mice and conferred rapid, full protection against lethal Y. pestis infection after a single dose. These data open avenues for urgently needed effective antibacterial vaccines.
Insights
This study developed an effective messenger RNA (mRNA) lipid nanoparticle (LNP) vaccine against plague by optimizing antigen design. A single dose provided full protection against lethal Yersinia pestis infection in mice.
Area of Science:
- Vaccinology
- Microbiology
- Immunology
Background:
- Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines are effective for viral pathogens.
- Limited data exist on mRNA-LNP vaccine effectiveness against bacterial pathogens.
- Antibiotic resistance necessitates alternative countermeasures for bacterial infections like plague.
Purpose of the Study:
- To develop an effective mRNA-LNP vaccine against the bacterial pathogen Yersinia pestis.
- To optimize mRNA payload and antigen design for antibacterial vaccine development.
- To evaluate the vaccine's immunogenicity and protective efficacy against plague.
Main Methods:
- Designed a nucleoside-modified mRNA-LNP vaccine encoding the Yersinia pestis F1 capsule antigen.
- Optimized mRNA guanine and cytosine content and antigen design.
- Assessed humoral and cellular immunological responses in C57BL/6 mice.
Main Results:
- The developed mRNA-LNP vaccine elicited significant humoral and cellular immune responses.
- A single dose conferred rapid and complete protection against lethal Yersinia pestis infection in mice.
- Demonstrated the potential of mRNA-LNP technology for antibacterial vaccine applications.
Conclusions:
- Optimized mRNA-LNP vaccine technology can be effective against lethal bacterial pathogens.
- This approach offers a promising new strategy for developing urgently needed antibacterial vaccines.
- The study paves the way for novel countermeasures against plague and potentially other bacterial diseases.
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