Potential option for rabies post-exposure prophylaxis: New vaccine with PIKA adjuvant against diverse Chinese rabies strains

Pengcheng Yu; Yuan Liu; Xiaoyan Tao; Ying He; Qian Liu; Bin Wang; Huiyu Zheng; Nan Zhang; Shengli Bi; Wuyang Zhu; Yi Zhang

doi:10.1016/j.vaccine.2023.10.001

Potential option for rabies post-exposure prophylaxis: New vaccine with PIKA adjuvant against diverse Chinese rabies strains

Vaccine. 2023 Oct 9:S0264-410X(23)01161-1. doi: 10.1016/j.vaccine.2023.10.001. Online ahead of print.

Authors

Pengcheng Yu¹, Yuan Liu², Xiaoyan Tao¹, Ying He¹, Qian Liu¹, Bin Wang², Huiyu Zheng², Nan Zhang², Shengli Bi³, Wuyang Zhu⁴, Yi Zhang⁵

Affiliations

¹ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, China.
² YishengBio Co., Ltd, Beijing, China.
³ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, China. Electronic address: bisl@ivdc.chinacdc.cn.
⁴ NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, China. Electronic address: zhuwy@ivdc.chinacdc.cn.
⁵ YishengBio Co., Ltd, Beijing, China. Electronic address: yi.zhang@yishengbio.com.

PMID: 37821317
DOI: 10.1016/j.vaccine.2023.10.001

Abstract

Rabies is a fatal zoonotic disease caused by the rabies virus. Despite existing vaccines, failures still persist. Complete protection relies on improving vaccination for delayed antibody response and weak cellular immunity. A more effective and secure vaccine is necessary for rabies prevention. For this purpose, we employed the use of PIKA adjuvant, a stabilized double-stranded RNA that interacts with TLR3, as an enhancer for the rabies immunization. Testing on mice infected with seven rabies strains prevalent in China showed over 80% protective efficacy without immunoglobulin. In contrast, the PIKA rabies vaccine exhibited a more significant enhancement in neutralizing antibody levels just 5 days post-vaccination, surpassing the immune response induced by licensed rabies vaccines. Furthermore, the administration of the PIKA rabies vaccine resulted in a significant augmentation in the population of T cells that produce IFN-γ in response to the antigen. Additionally, elevated levels of IL-1β, IL-6, CCL-2, and TNF-α were observed at the injection site. Furthermore, an increase in the levels of chemotactic proteins and pro-inflammatory molecules in the serum was observed following administration of the PIKA rabies vaccine. Confirmation of the mechanism of action of PIKA was further established by testing it on TLR3-knockout mice, proving that its adjuvant function is dependent on the TLR3 pathway. Taken together, these results indicate that the PIKA vaccine for rabies shows potential as a highly efficacious approach, resulting in a significant enhancement of the efficacy of rabies vaccines.

Keywords: Efficacy; PIKA adjuvant; Post‑exposure prophylaxis; Rabies vaccine; Rabies virus variants.