Rabies is a zoonotic virus transmitted from bites or scratches from infected animals, and it is among the most lethal of infectious diseases. Once clinical symptoms develop, mortality is almost 100%. Although current vaccine treatments are highly effective at preventing the onset of this disease, a few deaths still occur each year from rabies. In these instances, the post-exposure vaccine treatment most likely fails to elicit a sufficiently rapid production of antibodies and also fails to induce the strong cellular immunity needed to eliminate infected cells. Without an early and robust response to the vaccine, the host's central nervous system can be invaded by the virus, which leads to paralysis and ultimately death.

In a recent preclinical study Yi Zhang et al. tested the ability of a novel adjuvant, known as PIKA, to increase the efficacy of the rabies vaccine in mice (Virology 489, 165–172; 2016). PIKA is a stabilized chemical analog of double-stranded RNA that acts through Toll-like receptor 3 to enhance the presentation of antigens on antigen-presenting cells. This function, coupled with the release of pro-inflammatory cytokines through other pathways, enables PIKA to help induce non-specific immunity. Zhang et al. evaluated the ability of this PIKA rabies vaccine (PIKA-RV) to induce humoral and cellular immunity, finding that mice injected with PIKA-RV generated a titer of neutralizing antibodies that was almost 3-fold higher than that of mice injected with the rabies vaccine alone. They also found that T-cell activation, which is important for removing infected cells from the body, was also significantly higher in mice injected with PIKA-RV.

To test the level of protection conferred by PIKA-RV, beagles and golden hamsters were challenged with wild rabies virus and subsequently immunized with PIKA-RV or the vaccine alone. PIKA-RV protected 70% of beagles from the onset of disease, whereas the vaccine alone protected only 30% of beagles. In golden hamsters, the survival rates showed a similar trend, with 70% of hamsters surviving after immunization with PIKA-RV compared with about 20% survival with the vaccine alone.

Current treatments for rabies are successful in halting the onset of disease in most cases, but improvements in treatment regimens and survival rates are still needed, particularly in high-risk areas. Although these results with animal models await clinical-trial tests in humans, Zhang et al. have successfully demonstrated that PIKA-based enhancement of the rabies vaccine provides a potential new treatment for one of the most deadly infectious diseases.