Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
PLoS Negl Trop Dis. 2022 Aug 26;16(8):e0010699. doi: 10.1371/journal.pntd.0010699. eCollection 2022 Aug.
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.
吸血蝙蝠传播的狂犬病（VBR）仍然是拉丁美洲公共卫生和农业部门的一个持续负担，尽管几十年来一直通过捕杀蝙蝠种群来控制这种疾病。捕杀已被证明会驱散蝙蝠，导致狂犬病的传播加剧。因此，人们希望采用非致死性策略来控制 VBR，例如接种疫苗。在这里，我们评估了一种病毒载体重组嵌合糖蛋白狂犬病疫苗候选物（RCN-MoG）在墨西哥捕获并运往美国的未知狂犬病暴露史的吸血蝙蝠（Desmodus rotundus）中的安全性和有效性。RCN-MoG 疫苗接种被证明是安全的，即使在怀孕的雌性中也是如此，因为没有发现病变或不良反应的证据。我们在接种疫苗后的 28%（8/29）血清阴性蝙蝠中检测到狂犬病中和抗体。在狂犬病病毒（RABV）挑战后，成年蝙蝠的存活率比例为 55-100%，在治疗组、接种前后血清学状态和接种途径之间没有显著差异，而作为对照的 8 只幼崽（1-2.5 个月大）均因感染而死亡（P<0.0001）。重要的是，我们发现，即使感染导致致命，接种 RCN-MoG 似乎也能阻止病毒脱落。使用实时 PCR，我们在 10 只接种疫苗后因狂犬病而死亡的蝙蝠的唾液样本中均未检测到 RABV 核酸（一份结果不确定）。相比之下，在因疾病死亡的未接种疫苗的蝙蝠（14 只采样，包括一只不确定）的唾液样本中，71%（10/14 采样，加上一只不确定）检测到 RABV 核酸，包括幼崽。接种疫苗后血清转化率低和未接种疫苗的蝙蝠存活率高，可能是由于早期的自然暴露，限制了我们对疫苗效力的结论。然而，我们的发现表明，RCN-MoG 疫苗接种可能具有潜在的传播阻断作用，为拉丁美洲除长期捕杀计划之外控制 VBR 提供了一种有前途的策略。
