mRNA Vaccines Against Viruses
The mRNA vaccine platform has the capability to modulate the immune response via manipulating the targeted antigen, holding the great potential to develop rapid vaccines against emerging pathogens. Over the last 15 years, mRNA vaccine has evolved in synthesis, production, modification as well as delivery, leading to a revolution in the vaccine field. mRNA can be designed to encode various viral genes. After in vitro synthesis, mRNA encoding for a viral gene is administered into the host cell to instruct transient expression of the viral protein. Then, the host establishes an immune response and protective immunological memory to respond to the exogenous viral protein. To date, lipid nanoparticles (LNPs)are the most mature and commonly used mRNA delivery system. Various mRNA-LNP vaccines have been designed and developed against many diverse viruses in recent years, such as influenza virus, HIV, flavivirus, rabies virus (RABV), Ebola virus, Chikungunya virus (CHIKV), human Cytomegalovirus (HCMV), and the recent novel SARS-CoV-2.
mRNA vaccines against viruses
As one of the respiratory pathogens, influenza viruses can cause substantial morbidity and mortality, and thus have received public health concern worldwide. The mRNA vaccine has shown promise against influenza as a universal influenza virus vaccine with the capability to induce broad and long-lasting protective immune responses. Currently, there are two major types of mRNA vaccines against influenza viruses, including non-replicating mRNA vaccines as well as self-amplified mRNA (SAM) vaccines.
Despite the great progress in understanding the biology of HIV-1 infection, there is no licensed HIV vaccine on the market. Human immunodeficiency virus type 1 (HIV-1) is one of the most difficult vaccine targets and has several strategies to escape protective immune responses. At present, there are several preclinical and clinical studies of mRNA-based vaccines for the treatment of HIV, involving the direct use of injectable, formulated HIV mRNA vaccines in models and the ex vivo approach based on dendritic cells (DCs).
Flaviviruses belong to a diverse family of positive-sense, RNA viruses and are spread predominantly by arthropod vectors, having pandemic potential. mRNA vaccine as an ideal vaccine can lead to pan-flaviviral immunity by targeting conserved epitopes, such as conserved ENV dimer epitope. The mRNA vaccines have been developed against diverse flaviviruses, including vaccines against Zika virus (ZIKV), Dengue virus (DENV), and Powassan virus (POWV).
Rabies is a well-known zoonotic viral disease caused by the neurotropic rabies virus (RABV). The current rabies vaccines can’t meet the global need for effective and affordable vaccines due to the limitations in their production capacities, cost, as well as requirements of administration schedules and storage. Here, we focus on the mRNA vaccines developed against rabies and there are several factors to favor rabies mRNA vaccine development.
Ebola virus disease (EVD) caused by the Ebola virus (EBOV), is a life-threatening neglected tropical disease. The size and frequency of Ebola outbreaks have been dramatically increased in recent years due to the continuous human expansion into ecologies and the ubiquitous human migration. In recent years, both non-replicative and self-replicating mRNA vaccines have been developed against EBOV.
As one of Arthropod-borne virus (arbovirus), the Chikungunya virus (CHIKV) 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. Since the spread of CHIKV 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, including CHIKV.
Despite more than half a century of efforts to develop a human Cytomegalovirus (HCMV) vaccine, there is still no clinically licensed HCMV vaccine. In recent years, with a deeper understanding of HCMV-host interactions and scientific advances, the development of the HCMV vaccine is far advanced with numerous testing vaccine candidates, including mRNA-based vaccines. Based on the ability of the mRNA platform to deliver multiple mRNAs encoding various antigens in a single immunization, researchers developed an LNP encapsulating mRNA-based multiantigenic vaccine against HCMV.
Compared with traditional vaccines, mRNA vaccines have overwhelming advantages, including rapid development and their versatility. Given that mRNA vaccines have been shown to have good safety and strong immunogenicity against viruses in preclinical and clinical trials. Researchers chose mRNA-based technology to develop for COVID-19 vaccine. Over the past decade, mRNA-based technology has evolved in synthesis, production, modification as well as delivery, which has promoted mRNA-based technology as a promising vaccine platform. And the pandemic of COVID-19 also presents great opportunities for mRNA vaccine development.
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