Wu Xianfu, Yang Yong, Kling Chantal, Seigler Laurie, Gallardo-Romero Nadia F, Martin Brock E, Smith Todd G, Olson Victoria A
Centers for Disease Control and Prevention, Poxvirus and Rabies Branch/DHCPP/NCEZID, Atlanta, GA 30329, USA.
ARK Temporary Staffing, Lawrenceville, GA 30046, USA.
Vaccines (Basel). 2019 Jul 25;7(3):73. doi: 10.3390/vaccines7030073.
Rabies is preventable through vaccination, but the need to mount annual canine vaccination campaigns presents major challenges in rabies control and prevention. The development of a rabies vaccine that ensures lifelong immunity and animal population management in one dose could be extremely advantageous. A nonsurgical alternative to spay/neuter is a high priority for animal welfare, but irreversible infertility in one dose has not been achieved. Towards this goal, we developed a rabies virus-vectored immunocontraceptive vaccine ERA-2GnRH, which protected against rabies virus challenge and induced >80% infertility in mice after three doses in a live, liquid-vaccine formulation (Wu et al., 2014). To improve safety and use, we formulated an inactivated vaccine in a thermo-responsive chitosan hydrogel for one-dose delivery and studied the immune responses in mice. The hydrogel did not cause any injection site reactions, and the killed ERA-2GnRH vaccine induced high and persistent rabies virus neutralizing antibodies (rVNA) in mice. The rVNA in the hydrogel group reached an average of 327.40 IU/mL, more than 200 times higher than the liquid vaccine alone. The Gonadotropin-releasing hormone (GnRH) antibodies were also present and lasted longer in the hydrogel group, but did not prevent fertility in mice, reflecting a possible threshold level of GnRH antibodies for contraception. In conclusion, the hydrogel facilitated a high and long-lasting immunity, and ERA-2GnRH is a promising dual vaccine candidate. Future studies will focus on rabies protection in target species and improving the anti-GnRH response.
狂犬病可通过接种疫苗预防，但每年开展犬类疫苗接种活动的需求给狂犬病的控制和预防带来了重大挑战。开发一种能确保终身免疫且一剂就能实现动物种群管理的狂犬病疫苗可能极具优势。作为绝育手术的一种非手术替代方法，对动物福利而言是一个高度优先事项，但尚未实现一剂导致不可逆不育。为实现这一目标，我们研发了一种狂犬病病毒载体免疫避孕疫苗ERA - 2GnRH，该疫苗在以活液体制剂形式接种三剂后，可保护小鼠免受狂犬病病毒攻击，并诱导超过80%的不育（Wu等人，2014年）。为提高安全性和易用性，我们将灭活疫苗制成热响应壳聚糖水凝胶用于一剂接种，并研究了小鼠的免疫反应。水凝胶未引起任何注射部位反应，灭活的ERA - 2GnRH疫苗在小鼠体内诱导产生了高且持久的狂犬病病毒中和抗体（rVNA）。水凝胶组的rVNA平均达到327.40 IU/mL，比单独的液体制剂高出200多倍。促性腺激素释放激素（GnRH）抗体在水凝胶组中也存在且持续时间更长，但并未阻止小鼠受孕，这反映出GnRH抗体对避孕可能存在一个阈值水平。总之，水凝胶促进了高且持久的免疫反应，ERA - 2GnRH是一种有前景的双功能疫苗候选物。未来的研究将聚焦于目标物种的狂犬病保护以及改善抗GnRH反应。
