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Modeling The Lifecycle Of Ebola Virus Under Biosafety Level 2 Conditions With Virus-like Particles Containing Tetracistronic Minigenomes
Published on: September 27, 2014
Recombinant live attenuated measles virus-based vaccines inducing comprehensive protection against Ebola and Marburg
Junhui Zhou1, Xinghai Zhang2, Yanfeng Yao2
1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430062, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Filoviruses, including Ebola and Marburg viruses, present significant global health challenges due to their high mortality rates. Despite the availability of several Ebola virus vaccines, none provide cross-protection against multiple filovirus species. In this study, we developed recombinant live attenuated measles virus-based vaccine candidates designed to express Ebola or Marburg virus glycoproteins and generate virus-like particles for pan-filovirus immunization. The administration of these candidates by intraperitoneal injection into IFNAR-/- mice elicited robust antibody and cellular immune responses specific to Ebola and Marburg virus glycoproteins, with virus-like particles expressing candidates inducing the strongest immunity. Importantly, all vaccines containing Ebola virus glycoproteins afforded complete protection against mouse-adapted Ebola virus; meanwhile, those with Marburg glycoproteins provided protection against lethal replication competent vesicular stomatitis virus-Marburg virus challenges. These findings support the potential of measles virus-based vectors and virus-like particles as promising platforms for the development of vaccines targeting multiple filoviruses.
Insights
New measles virus-based vaccines show promise for broad protection against deadly filoviruses like Ebola and Marburg. These candidates generated strong immune responses and protected mice from lethal challenges, offering hope for pan-filovirus immunization.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Filoviruses, such as Ebola and Marburg viruses, pose significant global health threats due to their high fatality rates.
- Current Ebola virus vaccines lack cross-protection against other filovirus species, necessitating broader immunization strategies.
Purpose of the Study:
- To develop novel vaccine candidates using a recombinant live attenuated measles virus vector for pan-filovirus immunization.
- To evaluate the immunogenicity and protective efficacy of these measles virus-based vaccines against Ebola and Marburg virus challenges.
Main Methods:
- Development of recombinant measles virus vectors expressing Ebola or Marburg virus glycoproteins.
- Generation of virus-like particles (VLPs) from these vectors for enhanced immunization.
- Intraperitoneal administration of vaccine candidates in IFNAR-/- mice.
- Assessment of antibody and cellular immune responses.
- Challenge studies using mouse-adapted Ebola virus and vesicular stomatitis virus-Marburg virus.
Main Results:
- Vaccine candidates elicited robust, specific antibody and cellular immune responses against Ebola and Marburg virus glycoproteins.
- VLPs expressing vaccine candidates induced the strongest immune responses.
- All Ebola glycoprotein-containing vaccines conferred complete protection against mouse-adapted Ebola virus.
- Marburg glycoprotein-containing vaccines provided protection against lethal vesicular stomatitis virus-Marburg virus challenges.
Conclusions:
- Measles virus-based vectors and VLPs are promising platforms for developing pan-filovirus vaccines.
- These platforms can induce protective immunity against multiple filoviruses, addressing a critical unmet medical need.
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