Oral Vaccination With Recombinant Vesicular Stomatitis Virus Expressing Sin Nombre Virus Glycoprotein Prevents Sin Nombre Virus Transmission in Deer Mice.

Bryce M Warner,Rohit K Jangra,Bryan D Griffin,Derek R Stein,Kartik Chandran,Darwyn Kobasa,Gary P Kobinger,David Safronetz

doi:10.3389/fcimb.2020.00333

Abstract

Sin Nombre virus (SNV) is the major cause of hantavirus cardiopulmonary syndrome (HCPS) in North America, a severe respiratory disease with a high fatality rate. SNV is carried by Peromyscus maniculatus, or deer mice, and human infection occurs following inhalation of aerosolized virus in mouse excreta or secreta, often in peri-domestic settings. Currently there are no FDA approved vaccines or therapeutics for SNV or any other hantaviruses, therefore prevention of infection is an important means of reducing the disease burden of HCPS. One approach for preventing HCPS cases is to prevent the spread of the virus amongst the rodent reservoir population through bait vaccination. However, bait style vaccines for rodent-borne viruses have not been employed in the field, unlike those targeting larger species. Here we utilized a recombinant vesicular stomatitis virus expressing SNV glycoprotein precursor (rVSVΔG/SNVGPC) in an attempt to prevent SNV transmission. Vaccination of deer mice with rVSVΔG/SNVGPC was able to reduce viral RNA copy numbers in the blood and lungs of directly infected animals. More importantly, vaccination, either intramuscularly or orally, significantly reduced the number of transmission events in a SNV transmission model compared with control animals. This provides a proof-of-concept in which oral vaccination of deer mice results in protection against acquiring the virus following direct contact with infected deer mice. Further development of bait style vaccines for SNV or other rodent-borne viruses could provide an effective means of reducing disease burden.

Highlights

Hantaviruses are a family of enveloped, single stranded, negative sense RNA viruses that are part of the Order Bunyavirales (Jonsson et al, 2010)
hantavirus cardiopulmonary syndrome (HCPS) can be caused by a number of different hantaviruses, but predominantly due to infection with Sin Nombre virus (SNV) in North America and by Andes virus (ANDV) and Araraquara virus (ARAV) in South America (Figueiredo et al, 2014; Drebot et al, 2015)
We wanted to determine whether vaccination with rVSV G/SNVGPC could protect deer mice against infection with SNV

Summary

Introduction

Hantaviruses are a family of enveloped, single stranded, negative sense RNA viruses that are part of the Order Bunyavirales (Jonsson et al, 2010). Hantaviruses have a global distribution, with two phenotypically different diseases caused in Eurasia and the Americas. In Europe and Asia, hantavirus infection causes hemorrhagic fever with renal syndrome, while in the Americas, they are the cause of hantavirus cardiopulmonary syndrome (HCPS) (Jonsson et al, 2010). HCPS can be caused by a number of different hantaviruses, but predominantly due to infection with Sin Nombre virus (SNV) in North America and by Andes virus (ANDV) and Araraquara virus (ARAV) in South America (Figueiredo et al, 2014; Drebot et al, 2015). Disease is typified by general flu-like symptoms followed by sudden onset of cardiopulmonary involvement including cough, dyspnea, tachycardia, and more severe symptoms such as pulmonary edema, bilateral infiltrates, hypotension, and cardiogenic shock resulting in mechanical ventilation and intensive care treatment.

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Conclusion