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

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.

Oral Immunization with rVSV Bivalent Vaccine Elicits Protective Immune Responses, Including ADCC, against Both SARS-CoV-2 and Influenza A Viruses

“…Given that the oral deliveries of several rVSV-based vaccines have been reported to induce protective immune responses in animals [ 25 , 26 ], we wanted to extend the vaccination routes of our rVSV-based bivalent vaccine v-EM2/SPΔC1 Delta [ 28 ] to include oral immunization. To this end, we immunized female BALB/c mice with v-EM2/SPΔC1 Delta via oral cavity (oral, 1 × 10 6 50% tissue culture infectious dose, TCID 50 ) or intranasal (i.n., 1 × 10 5 TCID 50 ) routes in three groups ( n = 5 each group) for prime/boost: (1) i.n./i.n.…”

“…Also, it was reported that when the wild-type VSV is administered intranasally, its neurotoxicity is still a concern because it carries the potential for brain infection via the olfactory tract above the nose cavity [ 24 ]. While oral delivery of rVSV may carry a smaller risk than the intranasal route, it is worth noting that oral delivery of the rVSV vaccine has been reported to induce protective immune responses against the Sin Nombre virus and SARS-CoV-2 infection [ 25 , 26 ] The rVSV–Sin Nombre virus (SNV) vaccine was delivered to deer mice via oral gavages, in which the SNV glycoprotein (G) replaced the VSV-G to mediate vaccine entry into the mucosa [ 25 , 27 ] The rVSV-SARS2(+G) vaccine targeted the oral cavity mucosa through the VSV-G proteins that were incorporated in the virion’s surface (trans-complemented) and were responsible for the target cell tropism [ 26 ] We recently have reported a replication-competent rVSV-based bivalent vaccine (v-EM2/SPΔC1 Delta ) that effectively protected animals against both SARS-CoV-2 and the influenza A virus [ 28 ]. This bivalent vaccine has a modified Ebola virus glycoprotein (GP) that mediates rVSV entry to cells, including macrophages and dendritic cells (DCs).…”

Immune response during hantavirus diseases: implications for immunotherapies and vaccine design

“…151 Moreover, oral and intramuscular (IM) vaccination with a single dose of rVSVDG/SNVGPC reduced viral loads in the lungs and blood of Peromyscus maniculatus. 152 Remarkably, partial protection was achieved without inducing significant nAbs, but was enough to prevent SNV infection of uninfected/vaccinated animals when directly exposed to infected deer mice. 152 These data suggest the relevance of cellular immune mechanisms involved in the protection against hantavirus infection.…”

“…152 Remarkably, partial protection was achieved without inducing significant nAbs, but was enough to prevent SNV infection of uninfected/vaccinated animals when directly exposed to infected deer mice. 152 These data suggest the relevance of cellular immune mechanisms involved in the protection against hantavirus infection. Some of the most promising delivery approaches to date are nucleic acid-based vaccines, with several candidates currently advancing to clinical trials, as recently reviewed.…”

“…Interestingly, this vaccine also provided protection when administered 1 week before lethal ANDV challenge, in the absence of specific nAbs, suggesting other mechanisms of immunogenicity 151 . Moreover, oral and intramuscular (IM) vaccination with a single dose of rVSVΔG/SNVGPC reduced viral loads in the lungs and blood of Peromyscus maniculatus 152 . Remarkably, partial protection was achieved without inducing significant nAbs, but was enough to prevent SNV infection of uninfected/vaccinated animals when directly exposed to infected deer mice 152 .…”