Development of a Sin Nombre virus transmission model in deer mice and its use for assessing oral bait vaccine candidates

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Warner, Bryce Malcolm Thomas
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Hantaviruses are zoonotic viruses in the Order Bunyavirales, and cause two distinct diseases for which there are no approved vaccines or therapeutics. In the Americas, hantavirus infection causes hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35%. In North America, the primary agent responsible for HCPS is Sin Nombre virus (SNV) carried by Peromyscus maniculatus, or deer mice, and humans contract disease through exposure to the virus in contaminated rodent excreta and/or secreta. One major issue of working with certain hantaviruses is the need to propagate viral stocks in vivo within the virus’s natural host. Here we refined an infection protocol for developing viral stocks in vivo by utilizing intraperitoneal infection route as opposed to the classical intramuscular route. We also show that age and sex of deer mice has little effect on viral replication and shedding and that these factors are not an issue for viral stock production. We also developed a reliable experimental model of SNV transmission in deer mice. Transmission of SNV between deer mice is not well understood and the few studies that have attempted to examine transmission have either not been successful or have failed to shed light on how the virus is transmitted between animals. We show that direct contact is the main driver of SNV transmission rather than exposure to the virus in the environment, which is the case for human infection. Additionally, we use our developed transmission model to show that heat shock responses and changes in testosterone levels in SNV infected deer mice do not influence viral replication, shedding, or transmission. Finally, we used our transmission model to test the efficacy of vaccine platforms for protecting deer mice against acquiring SNV. Vaccination with rVSVΔG/SNVGPC was able to significantly reduce the risk of becoming infected with SNV in our model. Overall, we were able to develop a reliable SNV transmission model in deer mice and use this model to test various hypotheses on SNV ecology and to examine the protective efficacy of vaccines developed against SNV.
hantavirus, Sin Nombre virus, Deer Mice, Peromyscus maniculatus