Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

Joseph Prescott,Blair DeBuysscher,Heinz Feldmann,Kyle Brown

doi:10.3390/v6020516

Abstract

Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

Highlights

Andes virus (ANDV) is a New World hantavirus and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America, with case fatality rates of 30%–50%
Our laboratory has recently reported that a recombinant replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine, engineered to express the glycoprotein complex (GPC) of ANDV in place of the VSV glycoprotein (G), provides complete protection from disease in hamsters [8]
Hamsters vaccinated with VSV∆G-ANDV-GPC showed a statistically significant increase (p = 0.025) in survival when challenged with a lethal dose of ANDV 6 months after vaccination, with 5 of 6 of the vaccinated hamsters surviving challenge, whereas a single animal of the 6 unvaccinated hamsters survived ANDV challenge (Figure 1A)

Summary

Introduction

Andes virus (ANDV) is a New World hantavirus (family: Bunyaviridae, genus: Hantavirus) and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America, with case fatality rates of 30%–50%. ANDV is a zoonotic virus hosted by the long-tailed pigmy rice rat (Oligoryzomys longicaudatus) and upon transmission to humans, can cause HCPS [1,2]. The only animal model that recapitulates human disease caused by ANDV is the Syrian hamster [6,7]. Our laboratory has recently reported that a recombinant replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine, engineered to express the glycoprotein complex (GPC) of ANDV in place of the VSV glycoprotein (G), provides complete protection from disease in hamsters [8]. Hamsters were sterilely protected one month after a single dose of the vaccine upon challenge with a consistently lethal dose of ANDV. We sought to test the kinetics of the neutralizing response elicited by this vaccine and to test the duration of immunity following a single-dose vaccination to lethal disease caused by ANDV in the hamster model

Results and Discussion

Hamster Vaccination and Challenge

Andes Virus Neutralization and ELISA

Statistics

Biosafety and Ethics

Conclusions