4.5 Article

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

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VACCINE
卷 41, 期 46, 页码 6852-6862

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ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2023.10.001

关键词

Rabies vaccine; PIKA adjuvant; Efficacy; Rabies virus variants; Post-exposure prophylaxis

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Despite existing vaccines, failures in protecting against rabies still persist. In this study, the use of PIKA adjuvant as an enhancer for rabies immunization showed promising results in terms of antibody response and efficacy, surpassing licensed rabies vaccines in mouse models.
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-gamma in response to the antigen. Additionally, elevated levels of IL-1 beta, IL-6, CCL-2, and TNF-alpha 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.

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