Cimica et al.
A virus-like particle-based vaccine candidate against the tick-borne Powassan virus induces neutralizing antibodies in a mouse model.
Pathogens. 2021; 10:680. doi: 10.3390/pathogens10060680
In North America and Far Eastern Russia, sporadic infections caused by Powassan virus (POWV) are reported. POWV belongs to the “tick borne encephalitis virus serum complex” and was first discovered and isolated in Ontario, Canada, in 1958. The fatality rate of neuroinvasive POWV cases is about 10%, and 50% of the cases result in permanent long-lasting sequelae. Currently, neither a vaccine nor specific therapeutics are available. Two lineages of POWV have been identified: lineage 1 is transmitted by Ixodes cookei, while lineage 2, also called deer tick virus, is transmitted by I. scapularis.
A POWV vaccine candidate has been developed based on glycoprotein E (prM-E) and produced in a mammalian cell line (293T cells). Based on self-assembly, the recombinant protein forms virus-like particles (VLPs) and its structure resembles native virions with an icosahedral morphology typical for flaviviruses and sizes between 40 and 50 nm.
POWV-VLPS were produced and purified in large scale and analyzed for its immunogenicity in BALB/c mice. The antigen was injected three times by 3-week intervals, dosed with 1, 5 or 10 µg, and adjuvanted with a squalene-based oil-in-water nano emulsion (AddaVax).
After the second injection with 10 µg of antigen, complete seroconversion was observed through analysis by ELISA and after the second booster dose, complete seroconversion was also observed with the lowest antigen dose. In a neutralization assay it was shown that POWV-VLPs elicited high level of neutralizing antibodies in a dose dependent manner.
In addition, monoclonal antibodies against POWV were produced, which were reactive with POWV glycoprotein E antigen and POWV-VLPs, and which may represent potential candidates for therapeutic intervention against POWV infection.