A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus)

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.

Fig 1. Detection of rabies virus neutralizing antibodies (RVNA) in individual vampire bats at different time points after vaccination and challenge with a heterologous (coyote) strain of RABV in A) male vampire bats seronegative at baseline, B) male vampire bats seropositive at baseline, C) females, showing an additional timepoint sample 33 days after challenge with cRABV, and D) bats that were involved in the natural rabies outbreak (RABV strain of vampire bat origin).

In D, white-filled points represent three bats that died in the outbreak but were vaccinated and had a sample available for RVNA assessment. Events such as vaccination, the occurrence of a natural rabies outbreak within the captive colony, and the end of the study are indicated on the x-axis. Group size is indicated in parenthesis. The dotted line indicates the cut-off value of 0.06 UI/mL used in this study.

Fig 2. Kaplan-Meier analysis of vampire bat survival after challenge with a heterologous RABV strain and observation for 50 days post-challenge in A) male bats grouped by initial serostatus (seropositive/seronegative) and treatment received (vaccinated orally and topically, or control, RCN-luc), and B) female bats, seronegative-at-baseline and grouped by treatment received (vaccinated topically, in-contact, or no treatment).

Eight captive-born pups were considered RABV naïve controls. A P value of < 0.05 was set as significant and “ns” indicates no significance. The numbers of animals in each group are indicated.

Fig 3. Kaplan-Meier analysis of vampire bat survival after challenge with a heterologous RABV strain and observation for 50 days post challenge in vampire bats with rabies virus neutralizing antibody (RVNA), either naturally acquired or after vaccination, compared to vampire bats without RVNA.

A P value of < 0.05 was set as significant and “ns” indicates no significance. The numbers of animals in each group are indicated.