Epidemiology and biology of a herpesvirus in rabies endemic vampire bat populations

Megan E Griffiths,Alice Broos,Daniel J Becker,Ana Da Silva Filipe,Diana K Meza,Daniel G Streicker,Andrew Davison,Laura M Bergner,Carlos Tello

doi:10.1038/s41467-020-19832-4

Abstract

Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80–100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.

Highlights

Rabies is a viral zoonosis transmitted by vampire bats across Latin America
Preventing zoonoses by controlling transmission within natural animal reservoirs offers an exciting complement to ongoing efforts to manage these infections after they enter human and domestic animal populations
This study shows how integrating information from metagenomic sequencing, field studies and viral genomics can begin to overcome the logistic hurdles to managing zoonoses within inaccessible wildlife populations

Summary

Introduction

Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Despite the resounding success of these vaccination campaigns, similar attempts to target bats, the primary source of human rabies exposure in much of the Americas, face unresolved challenges Primary amongst these is finding a method of scalable vaccine delivery that achieves sufficiently high population-level coverage in remote and often inaccessible wild bat populations to alter viral transmission dynamics. Vaccines that spread unaided between individuals (‘transmissible vaccines’) have been proposed as a potential solution, since high population level coverage might be attained from a limited number of initial deployment efforts[13] Such vaccines are increasingly feasible to generate in the laboratory by engineering naturally present, replication competent viruses as vectors to express immunogenic proteins from the pathogenic virus of interest (hereafter, ‘target virus’)[14]. Ideal vectors should be benign, commonly occurring, host-specific viruses that can infect individuals that have already been infected by the wild-type version of the viral vector (i.e., capacity for ‘super-infection’)[14,15,19]

Methods

Results

Conclusion