A recombinant subunit Lassa virus vaccine elicits strong antibody responses

Abstract

Abstract Due to the epidemic potential and high case fatality rate, the WHO has declared the development of a Lassa virus (LASV) vaccine as a high priority for preventative use in endemic regions. We used a recombinant subunit vaccine platform to generate recombinant LASV glycoprotein (GP) in an insect cell expression system and tested its immunogenicity in an outbred mouse model. Briefly, LASV GP was secreted from a stably transformed Drosophila S2 cell line and the clarified culture supernatant was purified using immunoaffinity chromatography (IAC). SDS-PAGE gel analysis showed that the purity of the antigen was sufficient for immunogenicity testing. The eluted LASV GP was composed of GP1 and GP2 subunits, the GP1–2 heterodimer, as well as trace amounts of oligomer. Swiss Webster mice immunized intramuscularly with 3 doses of purified recombinant LASV GP, formulated with various adjuvants, showed maximal GP-specific antibody response after two immunizations. We concluded that we have successfully developed a production method for highly-purified, insect-cell expressed recombinant LASV GP capable of eliciting high antibody titers when formulated with a suitable adjuvant after only two doses. These results indicate the potential for recombinant GP to be an efficacious vaccine candidate. Further work on structural enhancements of the antigen and in-depth characterization of antibody and cell-mediated responses is ongoing.