Working towards a single-dose vaccine for rabies post-exposure prophylaxis.

Rabies is almost universally fatal if not treated before symptoms appear. Fortunately, post-exposure prophylaxis (PEP) is a nearly 100% effective treatment when started soon after rabies exposure. Nevertheless, rabies causes approximately 59,000 deaths annually, predominantly in rural parts of low- and middle-income countries. Current World Health Organization rabies PEP protocols require 1) a single administration of rabies immunoglobulin and 2) three or four doses of a vaccine administered over one to two weeks. The need for multiple healthcare visits significantly reduces treatment adherence due to financial, geographic, and other logistical barriers. Single-dose vaccine strategies represent a potential avenue to overcome these limitations by consolidating the vaccine dosing regimen into a single clinical interaction with a healthcare professional. This narrative review highlights several of the most promising technologies being used to pursue this goal, including mRNA vaccines, controlled-release formulations, and microneedle delivery systems. Although these strategies have yet to achieve clinical success in humans, data generated in preclinical studies and clinical trials offer insight into the limitations and potential benefits of these approaches as the field continues to seek a single-dose vaccine for PEP treatment. Highlighted articles were found by searching PubMed and Google Scholar, and published between January 2015 and August 2025.