ORCID

Document Type

Article

Abstract

Spillover of infectious diseases from wild animal populations constitutes a long-standing threat to human health for which few globally viable solutions have been developed. The use of oral baits laden with conventional vaccines distributed en masse represents one success story but is costly and practicable primarily for rabies risk reduction in North American and European carnivores. Efforts to expand vaccination to control pathogens within less accessible wildlife populations have raised interest in a new kind of vaccine capable of spreading pathogen-specific immunity through autonomous spread. However, such ‘transmissible’ vaccines raise concerns about the irrevocable release of genetically modified viruses into the environment. Herein, we explore the feasibility of an intrinsic strategy for transgene control within these vaccines based on the genetic destabilizing effect of cis-acting sequences flanking the heterologous transgene of interest. While suitable for the control of transgene stability within all types of DNA-viral vectored vaccines, this strategy has particular applicability to transmissible vaccines. Using a combination of experiments, mathematical modelling and whole-genome sequencing, we show that the rate of transgene loss can be controlled by varying the lengths of the direct repeat sequences. This opens a way for fine-tuning the lifespan of a transmissible vaccine in the wild.

Publication Date

2024-11-13

Publication Title

Proceedings of the Royal Society B: Biological Sciences

Volume

291

Issue

2034

ISSN

0962-8452

Acceptance Date

2024-10-11

Deposit Date

2026-11-05

Keywords

transmissible vaccines, vaccine safety, viral vaccine vector, virus evolution

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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