A group of researchers from Washington University School of Medicine have developed a method that could be used to produce vaccines for multiple, various flaviviruses, based on the mRNA of the chosen virus to be targeted. Because many flaviviruses are current or emerging pathogens, such as Zika virus, Dengue virus, and yellow fever virus, the ability to quickly and effectively produce a vaccine is a critical global health measure.

In a paper published this week in Cell Reports, titled, “An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections,” researchers from the lab of Michael Diamond, M.D., Ph.D., professor in the departments of medicine, molecular microbiology, pathology & immunology, demonstrate that a lipid nanoparticle-encapsulated mRNA vaccine against Powassan virus, an emerging tick-borne flavivirus, is highly immunogenic in mice and protects against lethal Powassan virus infection.

“We are excited that this mRNA-based vaccine against Powassan virus was highly immunogenic and conferred protection against multiple members of the family. We plan to continue studying the molecular basis for its broadly neutralizing antibody activity and test the vaccine against additional related viruses,” said Dr. Diamond.

The vaccine platform that the researchers used was previously developed for Zika virus. The lipid nanoparticle (LNP)-encapsulated modified mRNA encoding the structural premembrane (prM) and E protein genes. Co-expression of these proteins results in the secretion of subviral particles (SVPs) that share many features of the virus and an immune response that includes antibody production. The authors noted that the mRNA platform was used “because some mRNA have been reported to enhance follicular helper T cell and germinal center B cell responses that are needed to produce memory B cells and strong levels of antibodies.”

Furthermore, the vaccine induces a cross-reactive antibody response against multiple other tick-borne flaviviruses that protected mice against a distantly related Langat virus infection.

This graphic shows how a lipid nanoparticle-encapsulated mRNA vaccine protects mice against Powassan virus, as well as inducing a cross-reactive antibody response against other tick-borne flaviviruses. [Source: Vanblargen et al.]
Powassan virus is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for Powassan virus in certain regions of the northern U.S. (New York, Connecticut, and Wisconsin.)  Powassan virus infection causes life-threatening encephalitis. There is no vaccine or countermeasure available for prevention or treatment.

The authors noted that “the frequency of epidemics caused by emerging and re-emerging viruses, such as Zika virus, chikungunya virus, and Ebola virus, and the lack of preparedness for these public health crises highlight the need for the development of versatile vaccine platforms that can be rapidly manufactured and employed against various viral threats.” This LNP-encapsulated modified mRNA platform allows rapid development of vaccine candidates by insertion of the desired viral mRNA sequence into the coding region.”

Dr. Diamond and his colleagues hope that this could be a way to rapidly produce potential vaccines for new flaviviruses as they emerge and before they become epidemics.


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