학술논문

A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus).
Document Type
Article
Source
PLoS Neglected Tropical Diseases. 8/26/2022, Vol. 16 Issue 8, p1-21. 21p.
Subject
*RABIES vaccines
*VIRAL shedding
*BATS
*VACCINE effectiveness
*BAT diseases
*HIV seroconversion
*LYME disease
Language
ISSN
1935-2727
Abstract
Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats (Desmodus rotundus) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55–100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1–2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs. Author summary: Rabies is a fatal, zoonotic disease of global importance. In Latin America, the common vampire bat is responsible for most of the rabies outbreaks in livestock, and for decades, culling vampire bats has been an approach to control rabies. However, culling is not a sustainable practice, and non-lethal control strategies, such as the use of oral rabies vaccines, offer an alternative to manage the disease at the reservoir level. Our vaccine candidate, RCN-MoG, uses raccoon pox (RCN) as a viral vector for a mosaic gene expressing rabies glycoprotein (MoG). We orally or topically vaccinated wild-caught vampire bats with RCN-MoG and found that only a small proportion produced neutralizing antibodies after vaccination, and their survival to challenge with rabies virus (a measurement for vaccine protection) was not significantly improved compared to unvaccinated bats. Notably, however, vaccination with RCN-MoG had a blocking effect against viral shedding in the saliva of infected bats that succumbed to rabies. Our findings revealed a previously unknown but important benefit of vaccinating vampire bats: preventing viral shedding by rabid bats, which could reduce the spread of disease among bats and other animals. These observations should encourage further research, especially under field conditions. [ABSTRACT FROM AUTHOR]