mRNA-Based Chikungunya Vaccines
Arthropod-borne virus (arbovirus) is emerging as one of the major challenges to public health worldwide, as respective vectors extend their habitats. In addition to the Zika virus (ZIKV), the Chikungunya virus (CHIKV) transmitted by Aedes mosquitoes has recently attracted increased attention. The virus has recently broken out on an unprecedented scale, following regional outbreaks of the past few decades, which bring huge economic burden and immense suffering to the people in the affected regions. CHIKV causes an acute febrile illness referred to as Chikungunya fever (CHIKF). Since the spread of CHIKF is unprecedentedly rapid and wide, it is necessary to develop effective preventive measures. mRNA vaccine as a novel emerging vaccine platform has the capability to modulate the immune response via manipulating the targeted antigen, having the great potential to develop rapid vaccines against emerging pathogens. Here, we give a brief summary of CHIKV and mRNA-based CHIKV vaccines, highlighting that the mRNA-based technology is a promising vaccine platform for CHIKF prevention or treatment.
Chikungunya virus (CHIKV)
Similar to ZIKV, CHIKV was first isolated in Africa in 1952. CHIKV consists of a single-strand, positive-sense RNA and belongs to the genus Alphavirus of the Togaviridae family. The genome of CHIKV is composed of two open reading frames (ORFs) encoding one structural polyprotein (TF protein) and four non-structural proteins (nsPs). As an enveloped arbovirus, the virus is mainly transmitted by Aedes mosquitoes and Aedes albopictus. Chikungunya fever (CHIKF) is a recurrent infectious disease caused by the Chikungunya virus (CHIKV). Symptoms of this disease include high fever, arthritis, skin rash, and headache. Although most patients are able to recover from acute Chikungunya fever, there is a substantial subset of people experiencing a transition to severe joint pain that might last for months or years. In addition to the spread between humans and mosquitoes, the virus can also exist in purely enzootic cycles with non-human primates. So far, there are no specific treatments or vaccines available against CHIKV. Fortunately, CHIKV can lead to antibody responses, which can provide long-term, even lifelong protection. Therefore, the development of Chikungunya vaccines, especially mRNA vaccine, represents a promising strategy for disease control.
Antigens delivered by the most advanced vaccine candidates against ZIKV and CHIKV. (Schrauf, S., et al, 2020)
mRNA-based chikungunya vaccines
More and more research on CHIKV provides new methods and directions for the development of CHIKV vaccines. So far, the potential vaccine candidates against CHIKV can be divided into seven types, including subunit vaccine, inactivated vaccine, live-attenuated vaccine, virus-like particle vaccine, recombinant virus-vectored vaccine, chimeric vaccine, and nucleic acid vaccine. Among them, the mRNA vaccine represents one of the newest strategies in the development of CHIKV vaccine candidates. A company developed an mRNA vaccine (mRNA-1388) encoding CHIKV structural polyprotein. In the case of the mRNA CHIKV vaccine, mRNA instructs host cells to assemble virus-like particles (VLPs) as viral antigens for inducing immune response and generating antibodies accordingly. In a phase 1 trial, the evaluation of the Chikungunya vaccine candidate is now ongoing, involving its safety, tolerability, as well as immunogenicity.
Besides the above strategy, mRNA-based technology has been applied to passive immunotherapy. Based on the neutralizing human monoclonal antibody (mAb) isolated from the B cells of a Chikungunya survivor, researchers designed lipid nanoparticle (LNP)-mRNA to deliver mAb. CHKV-24, One human mAb, showed the most prominent inhibitory effect in neutralization assay in mice. Then researchers evaluated the protective capacity of CHKV-24 mRNA in mouse models of CHIKV infection and found that CHKV-24 mRNA protected mice from musculoskeletal tissue infection, arthritis, and death. Besides, viremia decreased to undetectable levels 2 days after inoculation.
Creative Biogene is a forward-looking research institute as well as a leading custom service provider in the field of mRNA-based drug research and development (R&D). Based on years of expertise in developing and optimizing mRNA molecules for medical purposes, we are now proud to offer a series of customized services to develop mRNA vaccines against infectious diseases. Our customers can contact our scientists directly for questions and learn about their project's progress at any time. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
References
- Kose, N., et al. (2019). “A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection.” Science immunology, 4(35).
- Schrauf, S., et al. (2020). “Current efforts in the development of vaccines for the prevention of Zika and Chikungunya virus infections.”Frontiers in immunology, 11.
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