Oxford's single-dose rabies vaccine is a promising step toward fighting the disease

The vaccine has passed its Phase 1 human trials with success.
Mert Erdemir
3D Illustration of rabies virus microscopic cells.
3D Illustration of rabies virus microscopic cells.EzumeImages/iStock

Rabies is a contagious virus that poses a serious threat to human life. While cases of rabies pop up across the world, it's especially widespread in parts of Africa and in India and China. The young are particularly vulnerable, with children under 15 account for roughly 40 percent of cases.

That's why a new, single-dose vaccine is such a big deal. Researchers at the University of Oxford report promising results from a Phase 1 clinical trial of their new rabies vaccine, ChAdOx2 RabG. This was the first time the new rabies vaccine was tested on human subjects.

With the RAB001 trial, the researchers aimed to observe the safety and the immune responses of the vaccine by analyzing levels of rabies neutralizing antibodies — a significant indicator of success in rabies vaccines. The study included 12 volunteer participants in total. Six of the subjects received a high dose of ChAdOx2 RabG while three received a medium dose, and another three of them received a low dose.

Strong immune responses against rabies

All the volunteers who got a medium or high dose developed levels of neutralizing antibodies that were the protective threshold of 0.5 International Units/ml, which is set by the World Health Organisation. That indicates a potent immune responses against rabies within two months of receiving the shot.

The long-term immune responses indicated the vaccine's effect is long-lasting. One year following vaccination, seven of the patients who recieved middle- or high-doses returned to the lab for an additional follow-up test. Six of them had neutralizing antibody levels over the protective threshold. This proves that the immune response from the vaccine is persistent.

"We’re absolutely delighted with these early results – the vaccine has performed even better than we had expected. The problems with existing rabies vaccines are that they are expensive and require multiple doses. We’re very hopeful that expanded trials in countries affected by rabies will prove that this new vaccine could enable routine, affordable, single-dose vaccination against this devastating disease for people living in such areas," said Associate Professor Sandy Douglas, Chief Investigator of the trial at the Jenner Institute, University of Oxford, in the press release published by the institution.

"New rabies vaccines based on modern vaccine technologies could become important tools in preventing the tens of thousands of rabies deaths that occur annually. Our strong early clinical trial data with ChAdOx2 RabG supports further development of this approach," added Dr. Daniel Jenkin, Lead Clinical Research Fellow of the trial at the same institute.

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Based on a genetically modified version of the common cold virus

The ChAdOx2 RabG vaccine is based on the ChAdOx2 vector, a genetically altered, weaker version of the common cold virus (adenovirus). And it's similar to the technology successfully applied in the Oxford-AstraZeneca COVID-19 vaccine.

The next plan of the researchers is to further develop the vaccine in light of the promising results from the RAB001 trial and pave the way for larger-scale clinical trials.

Currently, the team is conducting the Phase Ib/II clinical trial in Tanzania to evaluate safety and immunogenicity; findings from that trial are anticipated later this year, with final results due by the end of 2023.

The results of the study have been published in the journal The Lancet Microbe.


Rabies kills around 60 000 people each year. ChAdOx2 RabG, a simian adenovirus-vectored rabies vaccine candidate, might have potential to provide low-cost single-dose pre-exposure rabies prophylaxis. This first-in-human study aimed to evaluate its safety and immunogenicity in healthy adults. We did a single-centre phase 1 study of ChAdOx2 RabG, administered as a single intramuscular dose, with non-randomised open-label dose escalation at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Healthy adults were sequentially allocated to groups receiving low (5 × 109 viral particles), middle (2·5 × 1010 viral particles), and high doses (5 x 1010 viral particles) of ChAdOx2 RabG and were followed up to day 56 after vaccination. The primary objective was to assess safety. The secondary objective was to assess immunogenicity with the internationally standardised rabies virus neutralising antibody assay. In an optional follow-up phase 1 year after enrolment, we measured antibody maintenance then administered a licensed rabies vaccine (to simulate post-exposure prophylaxis) and measured recall responses. The trial is registered with ClinicalTrials.gov, NCT04162600, and is now closed to new participants. Between Jan 2 and Oct 28, 2020, 12 adults received low (n=3), middle (n=3), and high doses (n=6) of ChAdOx2 RabG. Participants reported predominantly mild-to-moderate reactogenicity. There were no serious adverse events. Virus neutralising antibody concentrations exceeded the recognised correlate of protection (0·5 IU/mL) in three middle-dose recipients and six high-dose recipients within 56 days of vaccination (median 18·0 IU/mL). The median peak virus neutralising antibody concentrations within 56 days were 0·7 IU/mL (range 0·0–54·0 IU/mL) for the low-dose group, 18·0 IU/mL (0·7–18·0 IU/mL) for the middle-dose group, and 18·0 IU/mL (6·0–486·0 IU/mL) for the high-dose group. Nine participants returned for the additional follow-up after 1 year. Of these nine participants, virus neutralising antibody titres of more than 0·5 IU/mL were maintained in six of seven who had received middle-dose or high-dose ChAdOx2 RabG. Within 7 days of administration of the first dose of a licensed rabies vaccine, nine participants had virus neutralising antibody titres of more than 0·5 IU/mL. In this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation.

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