DNA vaccination regimes against Schmallenberg virus infection in IFNAR^-/- mice suggest two targets for immunization

Schmallenberg virus (SBV) is an RNA virus of the Bunyaviridae family, genus Orthobunyavirus that infects wild and livestock species of ruminants. While inactivated and attenuated vaccines have been shown to prevent SBV infection, little is known about their mode of immunity; specifically, which components of the virus are responsible for inducing immunological responses in the host. As previous DNA vaccination experiments on other bunyaviruses have found that glycoproteins, as well as modified (i.e. ubiquitinated) nucleoproteins (N) can confer immunity against virulent viral challenge, constructs encoding for fragments of SBV glycoproteins G_N and G_C, as well as ubiquitinated and non-ubiquitinated N were cloned in mammalian expression vectors, and vaccinated intramuscularly in IFNAR^-/- mice. Upon viral challenge with virulent SBV, disease progression was monitored. Both the ubiquitinated and non-ubiquitinated nucleoprotein candidates elicited high titers of antibodies against SBV, but only the non-ubiquitinated candidate induced statistically significant protection of the vaccinated mice from viral challenge. Another construct encoding for a putative ectodomain of glycoprotein G_C (segment aa. 678-947) also reduced the SBV-viremia in mice after SBV challenge. When compared to other experimental groups, both the nucleoprotein and G_C-ectodomain vaccinated groups displayed significantly reduced viremia, as well as exhibiting no clinical signs of SBV infection. These results show that both the nucleoprotein and the putative G_C-ectodomain can serve as protective immunological targets against SBV infection, highlighting that viral glycoproteins, as well as nucleoproteins are potent targets in vaccination strategies against bunyaviruses.