Bunyavirus Vaccine Development
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Bunyavirus Vaccine Development
Increased human activity worldwide and rapid development of once rural areas have increased the potential for human-wildlife contact. Most bunyaviruses are zoonotic in origin, and outbreaks may result in significant loss of life, economic collapse, and social instability.
Overview of Bunyaviruses
In 2019, the International Committee on Taxonomy of Viruses (ICTV) updated the classification list of Bunyaviruses from Bunyaviridae to Bunyavirales to reflect the expanded diversity of these RNA viruses. As of 2023, the class Bunyaviricetes has been established and contains 2 orders, , 15 families, 4 subfamilies, 69 genera, and 592 species. Certain bunyaviruses, like Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), and Hantaan virus (HTNV), are highly virulent to humans and necessitate handling in a high biocontainment laboratory.
Genome of A Typical Bunyavirus
The typical structure of a bunyavirus particle has three nucleoprotein wrapped, negative-sense, single-stranded RNA segments, capped by RdRp. Virions contain three genome segments, small (S), medium (M), and large (L), and are coated by the Gn-Gc heterodimer. Each segment encodes its own set of proteins, and the core structural proteins common to all three-segment bunyaviruses are the nucleoprotein (N; encoded by the S segment), the Gn-Gc heterodimer (encoded by the M segment), and the RdRp (encoded by the L segment). The nonstructural proteins NSm and NSs are expressed by several rabbit viruses and are encoded by the M and S segments, respectively.
Typical structure of a bunyavirus particle. (Barker J.; et al., 2023)
Bunyavirus Vaccine
Appropriate vaccines are often the first choice for proactive prevention of viral infections. The table below shows the progress of research on some preventive programs currently under development against three highly pathogenic bunyaviruses: CCHFV, RVFV and HTNV.
| Type of Bunyaviruses | Type of Vaccines | Progress |
|---|---|---|
| CCHFV | Inactivated vaccines | Both VeroE6 cell line culture-inactivated vaccine (CCVax) and sucking mouse brain-inactivated vaccine (MBVax) induced humoral responses and dose-dependent protection, but CCVax showed a better effect. Inactivation with beta-propiolactone (BPL) may retain higher immunogenicity than inactivation with formalin |
| Subunit vaccines | Through in silico approaches, subunit vaccines are designed to cover all genotypes or most isolates. Traditional subunit vaccine approaches usually target the envelope glycoproteins Gn and Gc, or the more conservative NP of CCHFV. The use of different protein expression systems in producing subunit vaccines may also lead to different immune responses. However, these results await further validation in livestock. |
|
| VLP/VRP vaccines | VLPs have potential as vaccines to induce effective nAbs, but few have been reported. IFNAR-/- mice were fully protected 7 days after vaccination with a CCHFV VRP vaccine |
|
| DNA vaccines | A mixed DNA vaccine expressing CCHFV GP and NP showed high immune efficacy. It is notable that adjuvants are required for optimal protection of the DNA vaccines. | |
| mRNA | mRNA vaccine candidates expressing GnGc, NP, or GnGc+NP all elicited T-cell and B-cell responses and fully protected IFNAR-/- mice against CCHFV challenge. However, mRNA vaccines still require cold-chain storage and shipping. | |
| RVFV | Inactivated vaccines | The inactivated RVFV vaccine candidate has good immunological activity but mild side effects. |
| Attenuated vaccines | Mutation of NSs, deletion of non-structural protein NSm, G924S and A1303T mutations are of great significance for the attenuation of RVFV live vaccine. | |
| Subunit vaccines | Envelope glycoproteins Gn and Gc are the preferred target antigens for developing RVFV vaccines, especially the Gn head domain. | |
| VLP vaccines | VLPs composed of Gn and Gc combined with Stimune adjuvant prevent RVFV infection in mice. gag from retroviruses enhances VLP uniformity and quantity and can also serve as an adjuvant | |
| HTNV | Inactivated vaccines | Current research on inactivated HTNV vaccines focuses on generating strong long-term immune responses through a two-dose immunization strategy. |
| VLP vaccines | Modification of HTN-VLP can change the immunoglobulin response into a specific subtype and tend to be a Th1-type immune response. In particular, CD40L-VLP, which integrates HTNV GP with CD40 ligand (CD40L), brings better immune effects. | |
| Peptide vaccines | By modifying the peptide vaccine and synthesizing linear multi-epitope peptides, the protective effect of the vaccine was further improved and the viral RNA load in the spleen was reduced. However, further testing is still needed. |
How We Can Help
CD BioScience is an expert in the design, engineering, and production of VLPs. Leveraging our VLPlantTM platform, we are committed to helping our customers develop VLP vaccines against bunyaviruses. We provide customized services to meet our clients' unique needs. If you would like to know more, please do not hesitate to contact us.
Our services include but are not limited to:
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References
- Barker J.; et al., Mechanisms of bunyavirus morphogenesis and egress. J Gen Virol. 2023;104(4):10.1099/jgv.0.001845.
- Chen T.; et al., Advances and perspectives in the development of vaccines against highly pathogenic bunyaviruses. Front Cell Infect Microbiol. 2023 May 18;13:1174030.
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