Environmental distribution of certain modified live-virus vaccines with a high safety profile presents a low-risk, high-reward to control zoonotic diseases

Jennifer R Head,Julie Cleaton,Emily G Pieracci,Richard Chipman,Ad Vos,Jesse Blanton,Thomas Müller,Ryan Wallace

doi:10.1038/s41598-019-42714-9

Abstract

Oral vaccines aid immunization of hard to reach animal populations but often contain live-attenuated viruses that pose risks of reversion to virulence or residual pathogenicity. Human risk assessment is crucial prior to vaccine field distribution but there is currently no standardized approach. We mapped exposure pathways by which distribution of oral vaccines may result in inoculation into people and applied a Markov chain to estimate the number of severe adverse events. We simulated three oral rabies vaccination (ORV) campaigns: (1) first generation ORV (SAD-B19) in foxes, (2) SAD-B19 in dogs, and (3) third generation ORV (SPBN GASGAS) in dogs. The risk of SAD-B19-associated human deaths was predicted to be low (0.18 per 10 million baits, 95% CI: 0.08, 0.36) when distributed to foxes, but, consistent with international concern, 19 times greater (3.35 per 10 million baits, 95% CI: 2.83, 3.98) when distributed to dogs. We simulated no deaths from SPBN GAS-GAS. Human deaths during dog campaigns were particularly sensitive to dog bite rate, and during wildlife campaigns to animal consumption rate and human contact rate with unconsumed baits. This model highlights the safety of third generation rabies vaccines and serves as a platform for standardized approaches to inform risk assessments.

Highlights

While animal vaccination is an effective means of protecting human health through the reduction of zoonotic pathogens, vaccination of wildlife or free-roaming domestic animals through subcutaneous or intramuscular injection remains a challenge
Dashed arrows originating from one compartment and leading to a solid rate arrow indicate that the dynamic value within the compartment of origin directly influences the rate at which movement between the two different compartments occur
We developed and applied a novel method to compare the risk of various oral vaccines that can be used to aid planning of vaccination campaigns for wild or domestic animal populations

Summary

Introduction

While animal vaccination is an effective means of protecting human health through the reduction of zoonotic pathogens, vaccination of wildlife or free-roaming domestic animals (e.g. stray dogs) through subcutaneous or intramuscular injection remains a challenge. Second generation vaccine strains were developed through selection of monoclonal antibody escape mutants targeting the amino acid position 333 of the rabies glycoprotein rendering the rabies virus apathogenic in immune-competent mice even after direct intracerebral inoculation[22,23,24] Third generation vaccines, such as SPBN GASGAS, derived from the SAD complementary DNA (cDNA) clone[25], introduce further alterations through reverse genetics to eliminate the risk of reversion to virulence (i.e. vaccine-induced rabies) and have been proposed for use in both wildlife and free-roaming dogs[26,27]. In 2017, SPBN GASGAS, was approved for commercial use in foxes and raccoon dogs (Nyctereutes procyonoides) in Europe[30]

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