Malavé Carly M, Lopera-Madrid Jaime, Medina-Magües Lex G, Rocke Tonie E, Osorio Jorge E
U.S. Geological Survey, National Wildlife Health Center, Madison, WI 53711, USA.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Vaccines (Basel). 2021 Dec 4;9(12):1436. doi: 10.3390/vaccines9121436.
Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order ) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work.
狂犬病是一种古老的疾病，每年导致约59000人死亡。蝙蝠（翼手目）被认为是狂犬病病毒（RABV）的原始宿主，目前在美洲野生动物的狂犬病病例中占大多数。疫苗接种被用于控制狐狸和浣熊等其他野生动物宿主中的狂犬病，但尚无针对蝙蝠的狂犬病疫苗。我们之前开发了一种表达嵌合糖蛋白（MoG）基因的重组浣熊痘病毒（RCN）候选疫苗，在用RABV攻击时可保护小鼠和大棕蝠。在本研究中，我们开发了两种表达MoG的新型重组RCN候选疫苗（RCN-tPA-MoG和RCN-SS-TD-MoG），旨在改进RCN-MoG。我们评估并比较了它们在体外的表达、在体内的免疫原性以及在用RABV脑内攻击的接种小鼠中的保护效力。所有三种候选疫苗均诱导了显著的体液免疫反应，接种RCN-tPA-MoG或RCN-MoG显著提高了RABV攻击后的存活率。这些结果证明了在疫苗设计中考虑分子元件的重要性，并且接种RCN-tPA-MoG或RCN-MoG均可提供足够的保护以防止狂犬病感染，在未来的工作中，二者中的任何一种都可能是用于蝙蝠的充分的候选疫苗。
