Rabies is transmitted to humans typically through the bite or lick of an infected animal. Globally, more than three quarters of the human population is thought to be at risk for rabies exposure. Preventative vaccines are rarely used as they are not deemed to be cost effective for mass vaccination. Instead vaccines are given therapeutically following exposure. The vaccination regimen for post-exposure is complex and costly leading to either omission or inadequate use. In turn, it is estimated that worldwide rabies is responsible for ~55,000 deaths annually.
The recommended post-exposure rabies vaccination protocol, administered to approximately 15 million humans per year worldwide, consists of a series of five administrations spanning a 2-4 week period. In addition, the vaccine has to be combined with a hyperimmune serum to rabies, which is costly and in limited supply. Although extremely effective, the extended treatment course is problematic in many countries due to inadequate public health resources and limited access to treatment centers, especially in the rural areas of Africa, India and Asia, which also have a high prevalence of rabies in their wildlife and stray dog populations. In other countries such as those of South America, bat rabies is common and exposure is often ignored.
Dr. Ertl and colleagues have developed a novel rabies vaccine that produces long-lasting immunity from a single administration in primates. The vaccine is derived from recombinant chimpanzee adenovirus (rAdC68) that contains the DNA sequence of the rabies glycoprotein (rAdC68-rabies).
A single injection of rAdC68-rabies is sufficient to provide long-lasting immunity in non-human primates (see below). Importantly, the vaccine is less expensive to produce, maintain, and distribute than current human rabies vaccines. Due to these many benefits, the vaccine has the potential to render preventative childhood vaccination in high risk regions a reality.
Stage of Development
The rAdC68-rabies vaccine has been tested in non-human primates without pre-existing immunity to human adenovirus (1). Humans only rarely demonstrate neutralizing antibodies to such viruses (2). The researchers found the vaccine to be safe, immunogenic and efficacious.
Efficacy and immunogenicity: The vaccine induced rapid and long lasting rabies virus neutralizing antibodies (VNA). In fact, levels of ~1 international unit (IU) or greater were observed in all animals tested at the longest time point assayed, 21 months, following administration of 109 vps of rAdC68-rabies (VNA levels at or above 0.5 IU are critical for protection). Additionally, vaccination with rAdC68-rabies was found to induce memory responses as upon challenge with a dose of virulent canine rabies virus antibody titers increased on average of 240-fold as compared to pre-challenge titer.
Safety: None of the non-human primates tested showed adverse reactions to the rAdC68-rabies, even when given at 1011 vps, levels 100-fold greater than the amount required for long lasting protection.
The Wistar Institute is actively seeking a collaborator to facilitate the final stages of preclinical development and initiate clinical trials of the rAdC68-rabies prophylactic vaccine.
- Xiang et al. Virology 2014 450-451: 243-249. PMID: 24503087
- Chen et al. J. Virol. 2010 84(20):10522-32. PMID: 20686035