If you’ve attended a conference recently, followed international travel medicine updates, or spoken with colleagues working overseas, or read the rabies SmPC's, you may have heard that rabies pre-exposure vaccination ‘is now a two-dose schedule’. For many UK clinicians, this can be unsettling. It raises an immediate question: have we missed a major change?

The answer is no - but the situation reflects an important moment where scientific evidence, international policy, and national guidance are not fully aligned.

In 2022, the US Centers for Disease Control and Prevention (CDC), through its Advisory Committee on Immunization Practices (ACIP), updated its rabies pre-exposure prophylaxis (PrEP) recommendations. The long-standing three-dose schedule given on days 0, 7 and 21 or 28 was replaced with a simplified two-dose course administered on days 0 and 7. This decision was based on immunogenicity data demonstrating that two doses generate adequate neutralising antibody responses in immunocompetent individuals. The aim was to improve accessibility, reduce costs, and increase completion rates without compromising protection.

The CDC now describes this two-dose schedule as a complete primary course for individuals with short-term exposure risk, such as many travellers. For those with ongoing occupational risk, protection is maintained through booster doses or antibody titre monitoring.

However, this change has not been mirrored in the United Kingdom. Although the UK licencing includes provision for 0, 7 schedules, the Green Book (Chapter 27) continues to recommend the three-dose schedule as the standard primary course for rabies PrEP. There has been no formal adoption of the day 0 and 7 schedule as an equivalent primary regimen in UK guidance.

This distinction becomes particularly important when considering post-exposure management (PEP).

Under UK guidance, individuals who are fully vaccinated (pre-exposure) are managed differently to those who are unvaccinated or 'partially vaccinated' following a potential rabies exposure. Those with a complete recognised primary course do not require rabies immunoglobulin (RIG) and are instead managed with a reduced post-exposure vaccine schedule. This simplified response is one of the major practical advantages of pre-exposure vaccination.

However, UK post-exposure pathways (and those in some other countries too) are built around the assumption that a full primary course consists of three doses.

If a traveller presents having received a two-dose day 0 and 7 course abroad, the situation becomes less straightforward. While international guidance may consider this adequate primary immunisation, UK frameworks do not currently recognise it as such. In practical terms, this means that following an exposure, the individual may not be managed as fully vaccinated within UK post-exposure algorithms. This could also apply in other countries that have not adopted a two dose PrEP schedule, as well as the UK.

This has potential implications. A person who has received two doses may still mount a rapid immune response, and there is good evidence supporting the immunogenicity of this schedule. However, from a governance perspective, they may be treated as incompletely vaccinated under UK protocols. This could result in a recommendation for rabies immunoglobulin or extra doses of vaccine - a more complex intervention and sometimes quite difficult to source, especially if abroad.

In other words, the difference is not simply academic. The classification of “fully vaccinated” directly affects post-exposure management decisions.

This divergence reflects differing system priorities rather than disagreement about the science. The CDC model assumes ongoing risk assessment and follow-up through boosters or titre checks where required. The UK approach has traditionally prioritised durability of protection from the primary series itself, with less reliance on follow-up systems. The result is a more conservative definition of what constitutes complete pre-exposure protection.

For UK clinicians, this creates a growing grey zone. Travellers vaccinated abroad may reasonably believe they are fully protected after receiving two doses. Yet within UK frameworks, that course may be interpreted as partial. This does not mean the individual is unprotected, but it does influence how future exposures are managed.

For those delivering travel health advice in the UK, the most defensible position remains to initiate rabies PrEP using the three-dose schedule. At the same time, it is important to recognise that international schedules are evolving and to document clearly when vaccination has been undertaken under alternative frameworks.

Looking ahead, it is possible that UK recommendations will shift as simplified schedules gain wider acceptance. For now, however, we are in a transitional phase where science has evolved, some countries have adapted policy, and UK guidance has not yet changed. But it is entirely reasonable to acknowledge that the evidence base is evolving, even where policy has not yet changed.

A two dose schedule does not mean the individual is unprotected, but it does introduce uncertainty when advising on future travel risk, booster needs, or post-exposure management. From a governance perspective, UK clinicians remain accountable to national standards. Understanding this distinction allows clinicians to counsel travellers accurately - not only about protection before travel, but about how their vaccination history may influence post-exposure care in the future.

References

Centers for Disease Control and Prevention (CDC). (2022). Use of a 2-Dose Pre-exposure Prophylaxis Rabies Vaccination Schedule — United States, 2022. MMWR Morb Mortal Wkly Rep, 71(18): 619–627.

Centers for Disease Control and Prevention (CDC). (2024). Rabies Pre-exposure Prophylaxis. https://www.cdc.gov/rabies/hcp/pre-exposure-prophylaxis.html

UK Health Security Agency (UKHSA). (2022).Immunisation Against Infectious Disease (The Green Book) – Chapter 27: Rabies.

UK Health Security Agency (UKHSA). (2023). Rabies post-exposure treatment guidelines.

World Health Organization (WHO). (2018). Rabies vaccines: WHO position paper – April 2018. Weekly Epidemiological Record, 93(16).