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Circular RNA vaccines encoding fusion proteins of Mpox Virus A35R-M1R and B6R-A29L induce robust and durable
Xia Chuai1, Baoxin Zhao2, Yan Wu2
1State Key Laboratory of Virology and Biosafety, Center for Biosafety Mega Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430207, Hubei, China. chuaixia@wh.iov.cn.
Abstract:
Developing a safe and effective vaccine is crucial to control the recent worldwide outbreaks of mpox. Here, building upon our previously established lipid nanoparticle (LNP)-encapsulated circRNA vaccine platform, we constructed two bivalent mpox virus (MPXV) circRNA vaccines: cirBA encoding a B6R-A29L tandem antigen and cirAM encoding an A35R-M1R fusion antigen. Both bivalent MPXV circRNA vaccines, whether administered alone or in combination (designated cirMix), could induce robust and durable MPXV antigen-specific humoral and cellular immune responses in mice, conferring complete protection against lethal vaccinia virus Tian Tan strain (VTT) challenge. Moreover, even at low doses (2 µg for cirBA and cirAM, 4 µg for cirMix), all circRNA vaccines could provide 100% protection against lethal VTT challenge. Furthermore, at a higher dose (20 µg), all three vaccine groups induced potent long-term protective immunity lasting for at least 40 weeks, with cirBA achieving 100% protection, a level higher than that observed in the other groups. Collectively, our MPXV multivalent circRNA vaccines exhibit robust immunogenicity and represent promising candidates for further use in humans. The circRNA-based multivalent vaccine platform, capable of co-expressing multiple antigens, can be utilized for prevention of various infectious diseases.
Insights
New bivalent mpox virus (MPXV) circRNA vaccines demonstrated robust immunogenicity and complete protection against lethal vaccinia virus challenge in mice. This circRNA vaccine platform shows promise for preventing infectious diseases.
Area of Science:
- Vaccinology
- Virology
- Immunology
Background:
- Mpox outbreaks necessitate safe and effective vaccines.
- Lipid nanoparticle (LNP)-encapsulated circular RNA (circRNA) vaccines offer a promising platform.
Purpose of the Study:
- To develop and evaluate bivalent MPXV circRNA vaccines.
- To assess the immunogenicity and protective efficacy of novel MPXV circRNA vaccine candidates.
Main Methods:
- Construction of two bivalent MPXV circRNA vaccines: cirBA (B6R-A29L tandem antigen) and cirAM (A35R-M1R fusion antigen).
- Evaluation of immune responses (humoral and cellular) and protection against lethal vaccinia virus Tian Tan strain (VTT) challenge in mice.
- Assessment of vaccine efficacy at different doses and long-term durability of immune response.
Main Results:
- Both cirBA and cirAM, alone or combined (cirMix), induced robust, durable immune responses in mice.
- All circRNA vaccines conferred 100% protection against lethal VTT challenge, even at low doses (2-4 µg).
- High-dose vaccination (20 µg) provided long-term protection (>40 weeks), with cirBA showing superior efficacy.
Conclusions:
- MPXV multivalent circRNA vaccines are highly immunogenic and protective.
- The LNP-encapsulated circRNA platform is a versatile tool for developing vaccines against infectious diseases.
- These circRNA vaccines are promising candidates for human mpox prevention.
