HCMV mRNA Vaccines
The human Cytomegalovirus (HCMV), also known as human herpesvirus 5 (HHV-5), is the most common congenital infection worldwide, especially in low- and middle-income countries. HCMV infection is associated with significant morbidity and mortality in immunosuppressed patients. At present, vaccine development against HCMV is one of the major public priorities. Despite more than half a century of efforts to develop an 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 HCMV vaccine is far advanced with numerous testing vaccine candidates, including mRNA-based vaccines. Notably, HCMV vaccine candidates based on multi-antigen approaches hold the potential to maximize induced protective immunity, thus, it is most likely to succeed in HCMV vaccine development.
Human Cytomegalovirus (HCMV)
The human Cytomegalovirus (HCMV) is an enveloped, double-stranded DNA β-herpesvirus belonging to the Betaherpesvirinae subfamily. Similar to other herpesviruses, the virion of HCMV is a quasi-spherical shape, which is composed of a double-stranded DNA (dsDNA) genome, an icosahedral capsid, a proteinaceous layer and a coating.
As the most common congenital infection worldwide, HCMV infection has been reported in 40-60% of the population in industrialized countries and up to 80-100% of the population in developing countries. HCMV establishes lifelong infection in the host, which is associated with poor hygiene standards, low household income and older age. Generally, HCMV infection in the immunocompetent population is asymptomatic. However, HCMV causes severe complications and high mortality in immunocompromised individuals and neonates with congenital infections. HCMV can be transmitted from person to person through body fluids, including saliva, urine, breast milk, tears, and so on. In addition, HCMV can be directly transmitted through the placenta to the fetus. As a congenital infection, HCMV usually leads to hearing loss in childhood, and sometimes causes mental retardation, vision loss, microcephaly, hepatosplenomegaly and other congenital sequelae.
Structure of HCMV virion. (Gugliesi, F., et al, 2020)
mRNA-based HCMV vaccines
Based on the ability of the mRNA platform that is able to deliver multiple mRNAs encoding various antigens in a single immunization, researchers developed an LNP encapsulating mRNA-based multiantigenic vaccine encoding five constituents of pentameric complex (PC), glycoproteins gB, and tegument phosphoprotein 65 (pp65). The preclinical study demonstrated that this vaccine induced potent humoral and cell-mediated immune responses in animal models. Among them, gB and pp65 belong to vectored genes of HCMV, and they are target antigens of many vaccine candidates.
A recent study demonstrated that a HCMV gB nucleoside-modified mRNA vaccine induced a more durable and broader antibody response when compared with the MF59-adjuvanted gB protein immunization. The LNP mediated gB nucleoside-modified mRNA vaccines were tested on young New Zealand White rabbits. Results showed that this vaccine was comparable to the gB/MF59 subunit vaccine in terms of kinetics, peak gB-binding, and functional antibody responses. While there was a significantly longer duration of antibody responses using the LNP mediated nucleoside-modified mRNA. These preclinical data suggested that this vaccine is a viable immunization strategy for HCMV infections and needs to be further evaluated in preclinical models.
With major advantages that rapid and scalable mRNA platform has the potential to encode any antigen, modified mRNA formulated with lipid nanoparticle (LNP) has emerged as an attractive platform for vaccines and therapeutics. 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
- Gugliesi, F., et al. (2020). “Where do we Stand after Decades of Studying Human Cytomegalovirus?.” Microorganisms, 8(5), 685.
- Nelson, C. S., et al. (2020). “Human cytomegalovirus glycoprotein b nucleoside-modified mrna vaccine elicits antibody responses with greater durability and breadth than mf59-adjuvanted gb protein immunization.” Journal of virology, 94(9).
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