Inactivated Rabies Virus-Vectored Immunocontraceptive Vaccine in a Thermo-Responsive Hydrogel Induces High and Persistent Antibodies against Rabies, but Insufficient Antibodies against Gonadotropin-Releasing Hormone for Contraception.

Victoria A. Olson,Nadia F. Gallardo-Romero,Yong Yang,Xianfu Wu,Todd G. Smith,Brock E. Martin,Laurie Seigler,Chantal Kling

doi:10.3390/vaccines7030073

Abstract

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.

Highlights

To control rabies in dogs, vaccination is the key strategy
Human behavior and dog behavior are both important in rabies control
In order to provide an option for rabies control under those conditions, we have been working on the development of a dual vaccine for long-lasting rabies protection and animal population management [9,10,11]

Summary

Introduction

Dog rabies vaccine is one of the “core vaccines” in veterinary practice, and the vaccination schedule should be strictly followed [1]. If there is a skip or noncompliance during the schedule, vaccination will be reevaluated or reinitiated. This practice is costly and requires a high level of responsible dog ownership. Rabies has been well controlled in many countries through this practice. In developing countries where rabies is enzootic, many dogs are owned but free roaming [4]. The ultimate goal of our research is to protect against rabies in dogs with only one vaccination and simultaneously mitigate reproductive behaviors in free-roaming dogs. The goal is ambitious, and has not been intensively explored due to technical challenges

Objectives

Methods

Results