Inactivated rabies vaccines are used for active immunisation. After administration, the body is stimulated to produce antibodies against the rabies virus. Active immunisation is used as part of pre-exposure prophylaxis (before a potential rabies risk contact, e.g. as a travel vaccination) and as part of post-exposure prophylaxis (after a rabies risk contact has taken place).

In contrast, the administration of rabies antibodies (also known as "human rabies immunoglobulin" [HRIG]) is a form of passive immunisation in which antibodies against the rabies virus are administered directly to the patient. The aim of passive immunisation is to bridge the period until the body's own antibodies are produced after active immunisation. In contrast to active immunisation, passive immunisation is only necessary in special situations after a rabies risk contact as part of post-exposure prophylaxis.

As part of active immunisation, inactivated rabies vaccines are used both for pre-exposure prophylaxis (before a potential rabies risk contact, e.g. as a travel vaccination) and for post-exposure prophylaxis (after a rabies risk contact has taken place). Nowadays, these are mostly so-called cell culture vaccines, in which rabies viruses are cultivated on human or animal cells and then inactivated. Cell culture vaccines have replaced the previously used nerve tissue vaccines.

Two inactivated rabies vaccines are available in Austria: Rabipur®, a cell culture vaccine based on chicken embryonic cells, and Verorab®, a cell culture vaccine based on Vero cells. The human Rabies immunoglobulin Berirab® is available in Austria for passive immunisation.

The drug safety of commercially available rabies vaccines is considered excellent, vaccination reactions such as local reactions at the vaccination site, headaches, fatigue, general feeling of illness, fever and dizziness are possible but short-lived. All known possible side effects are also listed in the instructions for use of the vaccine preparation used, together with the approximate frequency with which they may occur. Information on possible side effects, interactions and contraindications can also be obtained from the doctor treating you.

If there is a known risk of a severe allergy to the vaccine or one of its components, a different rabies vaccine that does not contain this component can be administered. This is an individual decision that must be made by the attending physician in each individual case.

A chicken protein allergy is not an absolute contraindication to the administration of Rabipur® vaccine containing chicken protein. It can therefore be administered under observation. However, if an alternative, chicken protein-free preparation is chosen, the rabies vaccine Verorab® produced in Vero cells or the HDC vaccine produced in human diploid cells can be used, for example. As the HDC rabies vaccine is not available in Austria, it must be obtained from abroad if necessary, e.g. from the International Pharmacy (Kärntner Ring 17, 1010 Vienna, +43 1 5122825). (14).

Both active and passive immunisation (inactivated rabies vaccine or immunoglobulin) have proven to be safe and effective during pregnancy and breastfeeding. Particularly due to the severity of rabies infection and the lack of treatment options for the disease, post-exposure prophylaxis according to the category of contact must also be carried out after a rabies risk contact during pregnancy and breastfeeding. In the case of pre-exposure prophylaxis (before a potential rabies risk contact, e.g. as a travel vaccination), an individual risk-benefit assessment must be carried out in consultation with the attending physician.

The same preparations are used for children and adults for both active and passive immunisation (inactivated rabies vaccine or immunoglobulin). There are no separate rabies vaccines for children. The respective dosage can be found in the instructions for use of the medicine used.

If possible, the same vaccine should be used for basic immunisation. This also applies to the vaccination series in the course of post-exposure prophylaxis.

In principle, all modern cell culture rabies vaccines are interchangeable, but a change of vaccine is an off-label application. If such a change is unavoidable (e.g. due to vaccine supply bottlenecks or due to post-exposure prophylaxis started abroad with a different vaccine and continued in Austria), this can be done after careful risk-benefit assessment and information on off-label use.

In the event of a change of vaccine, it is important that the respective vaccination schedule is retained.

Vaccines commonly used in other countries that are compatible with Rabipur® or Verorab® are, for example, HDC vaccines (Human Diploid Cell Culture Rabies Vaccine, HDCV) or PDE vaccines (Purified Duck Embryo Vaccine, PDEV).

Vaccines based on nerve tissue (e.g. Suckling Mouse Brain Vaccine, SMBV) are not compatible, but their production is gradually being discontinued due to an unfavourable side-effect profile and a comparatively poor immune response.

A pre-exposure rabies vaccination is recommended before travelling to a rabies endemic area. In particular, travellers who undertake outdoor activities (e.g. cycling, hiking) in rabies endemic areas or who travel to remote areas where prompt medical care cannot be guaranteed should receive a series of vaccinations before starting their journey.

For stays in Austria, pre-exposure rabies vaccination is only recommended for people who could be occupationally exposed to rabies. This includes personnel from the fields of veterinary medicine and animal care (including students of veterinary medicine, taxidermists, animal keepers, animal dealers), forestry and agriculture, the military and disaster relief services, the judicial/prison service, epidemic hygiene, the relevant laboratories and vaccine production facilities as well as bat researchers and cave explorers. For hunters, rabies prophylaxis is only indicated for hunting stays in rabies-endemic foreign countries or in border areas to rabies-endemic areas, whereby the border areas of Austria to its neighbouring countries are currently not to be counted as rabies-endemic areas.

• Conventional schedule: one vaccination (0.5 or 1 ml i.m. depending on the manufacturer's instructions) on days 0, 7 and 21-28 (for all age groups).
• Rapid schedule: one vaccination (0.5 or 1 ml i.m. depending on the manufacturer's instructions) on days 0, 3 and 7 (for people aged between 18 and 65 if the conventional schedule is not feasible due to time constraints).
• Alternative fast-track schedule (off-label use): one vaccination each (0.5 or 1 ml i.m. depending on the manufacturer's instructions) on days 0 and 7 (only for immunocompetent persons). According to the Austrian vaccination plan, completion of the basic immunisation by a third vaccination after one year is recommended if future travel to rabies endemic areas cannot be ruled out.

Due to the often limited availability of rabies immunoglobulin in some rabies endemic areas, the Austrian Vaccination Plan recommends that travellers be vaccinated i.m. at least once before departure if indicated (off-label use), as this can achieve a sufficient and effective antibody response in healthy adults through subsequent post-exposure rabies prophylaxis.

According to the World Health Organisation (WHO), in exceptional cases (e.g. if there is a shortage of vaccine), intradermal application can be used instead of intramuscular application. In the conventional regimen and the rapid regimen, 0.1 ml is administered intradermally on each of the three days. In the alternative rapid regimen, two doses (on the left and right arm) of 0.1 ml each are administered intradermally on days 0 and 7.

However, the correct intradermal application of the vaccine requires practice and should therefore only be used in exceptional cases. If applied correctly, the immune response can be expected to be just as good as with intramuscular application.

For pre-exposure prophylaxis, immunocompromised persons should always be vaccinated in a three-vaccination schedule. In addition, a vaccination success check (determination of the antibody titre by means of a neutralisation test) should be carried out 4-8 weeks after the third vaccination. Depending on the result of the vaccination success check, these persons are to be categorised as immunosuppressed persons or not in the event of a rabies risk contact when selecting the required PEP vaccination schedule.

According to the WHO, routine booster vaccinations are not necessary for the general population after basic immunisation, as the booster can last for decades or even a lifetime. This means that a rapid immune response is induced by the administration of a post-exposure vaccination after risk contact with rabies, regardless of how long ago the basic immunisation took place.

However, people travelling to rabies-endemic areas with poor vaccine availability should have a contact-independent booster vaccination as a precautionary measure before travelling if the basic immunisation was more than 2-5 years ago. Furthermore, people who are exposed to an ongoing risk of rabies (e.g. occupationally exposed persons) should regularly receive a booster vaccination depending on their antibody levels.

Persons who are exposed to an ongoing risk of rabies due to their profession should have their rabies antibody levels checked regularly (titer controls). The interval should be determined on the basis of an individual risk evaluation. If titer checks are not possible, a booster vaccination can alternatively be carried out every two to five years, regardless of the antibody level.

If in doubt, people travelling to rabies-endemic areas with poor vaccine availability can also have a serological vaccination success test carried out before travelling.

In exceptional cases, a check of the rabies antibody level is also indicated after post-exposure prophylaxis.

Post-exposure rabies prophylaxis refers to measures that are intended to prevent infection with the rabies risk after a rabies risk contact has taken place. Essentially, post-exposure rabies prophylaxis consists of three pillars: wound care, active immunisation and passive immunisation. The extent of post-exposure rabies prophylaxis should be selected depending on the type of contact that has taken place or the animal species.

To assess the indication for post-exposure rabies prophylaxis following contact with an animal, it is necessary to evaluate whether the contact was a rabies risk contact or not. The following aspects must be assessed: geographical localisation of the exposure or country of origin of the animal, type of animal and type of contact.

After rabies risk contact has taken place, wounds (bite wounds, scratches) should be treated immediately as part of post-exposure rabies prophylaxis by thorough washing and rinsing with soap and plenty of water and/or virucidal disinfectant (at least 15 minutes in total). This should reduce the penetration of the rabies virus at the wound site. The need for additional wound care (trauma surgery, antibiotic/analgesic therapy, tetanus vaccination) must be evaluated by the attending physician.

Active immunisation as part of post-exposure rabies prophylaxis is the administration of rabies vaccines (inactivated rabies vaccines) after a risk contact with rabies has taken place. After administration, the body is stimulated to produce antibodies against the rabies virus. This prevents infection as far as possible in the event of a rabies risk contact.

Passive immunisation as part of post-exposure rabies prophylaxis is the administration of rabies antibodies (human rabies immunoglobulin, HRIG). Passive immunisation is always carried out in parallel with active immunisation in previously unvaccinated persons and aims to bridge the time until the body's own antibody formation after active immunisation. In contrast to active immunisation, passive immunisation is only necessary in special situations after a rabies risk contact as part of post-exposure prophylaxis.

The required number of vaccine doses to be administered as part of post-exposure rabies prophylaxis (PEP) depends on whether or not the person concerned has previously received immunisation against rabies.

Persons who have previously received full basic immunisation are given two vaccinations (one vaccination each on days 0 and 3) (= shortened PEP schedule). This also applies to people who have had their basic immunisation some time ago.

A full PEP schedule must be administered to people who have not received basic immunisation or have received incomplete basic immunisation. This can be administered either as a so-called "Essen schedule" with one vaccination each on days 0, 3, 7, 14 and 28 (five vaccine doses in total) or as a so-called "Zagreb schedule" with two vaccinations on day 0 (one in the right arm and one in the left arm) and one vaccination each on days 7 and 21 (four vaccine doses in total).

However, according to the recommendations of the World Health Organisation (WHO), the fifth vaccination on day 28 as part of the meal schedule can be omitted for healthy, immunocompetent persons, provided that optimal conditions for wound care and post-exposure rabies prophylaxis have been met.

Persons who have been immunised in the following schedules are considered fully immunised:

• Conventional schedule with three vaccine doses (on days 0, 7, 21-28)
• Fast-track schedule with three vaccine doses (on days 0, 3, 7)
• Alternative fast-track schedule with two vaccine doses (on days 0, 7)
  • Within one year after 2nd dose: people are considered fully immunised
  • After one year following the 2nd dose: People are only considered fully immunised if a third vaccination has been given after one year to complete the basic immunisation
• Post-exposure prophylaxis with at least three of the five vaccinations in the Essen or complete Zagreb schedule

Passive immunisation (administration of a rabies immunoglobulin) should always be carried out after a category III rabies risk contact. In addition, persons with immunodeficiency should also receive passive immunisation after a category II rabies risk contact.

In immunocompetent persons who have previously received at least two doses of a rabies vaccine, immunoglobulin is no longer administered in the event of a suspected rabies contact, regardless of the category of exposure.

If post-exposure prophylaxis is to be repeated in the case of an exposure that occurred more than one year ago, only active immunisation is carried out rather than passive immunisation, even if this is indicated.

If possible, the immunoglobulin should be administered on the same day as the first immunisation. It can be given up to and including the seventh day after the start of active immunisation. Administration more than 7 days after the first vaccination dose or more than one day after the second vaccination dose is no longer indicated.

After a risk contact in Austria with a mammal (e.g. dog or cat) that has been imported from a rabies endemic area and has no proof of a rabies vaccination (illegal import), post-exposure prophylaxis is indicated according to the category of the contact that took place. In the case of dogs and cats, post-exposure prophylaxis can be discontinued if the animal is within reach and remains healthy during an observation period of ten days.

Especially when travelling, it may not always be possible to adhere exactly to the recommended vaccine intervals for post-exposure prophylaxis. If the vaccination schedule has not been adhered to exactly, for example because a dose was administered late, it is not absolutely necessary to restart a vaccination series in the respective schedule. The prerequisite for this is that the first three doses of vaccine do not deviate from the recommended schedule by more than one day. In all other cases, the vaccination schedule must be restarted.

In principle, post-exposure rabies prophylaxis should be carried out as soon as possible after a rabies risk contact. As incubation periods (period between infection and outbreak of the disease) of more than one year have been described for rabies in humans, active immunisation as part of post-exposure rabies prophylaxis should in principle be administered even if the rabies risk contact occurred months or years ago. However, if the exposure occurred more than a year ago, human rabies immunoglobulin (passive immunisation) should no longer be administered, but only active immunisation should be carried out.

As there is no treatment for rabies, post-exposure prophylaxis (PEP) is of crucial importance. A prerequisite for the success of post-exposure prophylaxis is that it is administered promptly. For this reason, it is not permissible to wait with the administration if there is an appropriate indication. In particular, it is not permissible to wait for the results of rabies tests on the animal.

In the event of a rabies risk contact with a dog or cat that is within reach (owner known and contactable), consideration may be given to ending post-exposure rabies prophylaxis after ten days, provided the animal has remained healthy throughout the observation period. This procedure only applies to dogs and cats. In addition, post-exposure rabies prophylaxis can be terminated if the dead animal (applies to all animals suspected of having rabies) has tested negative for rabies.

No further active or passive immunisation is required in the event of renewed rabies risk contact within three months of complete post-exposure prophylaxis. Only appropriate wound care is required. This does not apply to persons with immunodeficiency.

If an immunocompromised person has previously received pre-exposure prophylaxis and a vaccination success control with a proven antibody titre of > 0.5 IU/ml (determined in the neutralisation test) is available, the procedure for post-exposure prophylaxis for these persons is the same as for immunocompetent persons.

If the person has never previously been immunised against rabies, if there is no vaccination success control or if the antibody titre was < 0.5 IU/ml (determined in the neutralisation test), the Essen schedule (0, 3, 7, 14 and 28) is used for post-exposure prophylaxis in these persons, with the difference that an additional vaccination dose can be administered on day 0. In addition to active immunisation, passive immunisation is indicated for this group of people with both category II and III exposure.

As immunosuppression can lead to a reduced immune response, an antibody test on the day of the last vaccine dose is recommended. If the titre falls below 0.5 IU/ml (determined in the neutralisation test), further vaccine doses should be administered immediately. In any case, a specialist in internal medicine or clinical immunology should be contacted.

In Austria, post-exposure rabies prophylaxis (active and passive immunisation) is carried out free of charge by the national rabies vaccination centres responsible for this.

Federal Ministry of Social Affairs, Health, Care and Consumer Protection (BMSGPK). Vaccination Plan Austria 2023/2024. Version 2.0 (as of 14 May 2024). Vienna: BMSGPK; 2024.

World Health Organisation (WHO): Rabies. Available online at: https://www.who.int/en/news-room/fact-sheets/detail/rabies (last accessed on: 08/08/2023).

Robert Koch Institute (2022): Rabies. RKI guidebook. Available online at: https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Tollwut.html (last accessed on: 08/08/2023).

World Health Organisation (WHO). Rabies Vaccines: WHO Position Paper - April 2018. 2018. Weekly Epidemiological Record, No 16, 2018, 93, 201-220.

Jackson A, Wunner W. Rabies. Scientific Basis of the Disease and Its Management. 2nd edition. London: Academic Press; 2007.

Russell K, Brown K. UKHSA guidelines on managing rabies post-exposure (January 2023). UK Health Security Agency; 2023.

World Health Organisation. FAQs: Frequently asked questions on rabies. WHO Regional Office for South-East Asia. New Delhi: WHO; 2013.

Fitzpatrick JL, Dyer JL, Blanton JD, Kuzmin IV, Rupprecht CE. Rabies in rodents and lagomorphs in the United States, 1995-2010. J Am Vet Med Assoc. 2014;245(3):333-7.

Standing Vaccination Commission and German Society for Tropical Medicine, Travel Medicine and Global Health e.V. with special contributions from Kling K, KülperSchiek W, Rothe C, Boecken G, Bogdan C, Feldt T, Köhler C, Ledig T, Löscher T, Meerpohl J, Mertens T, Ramharter M, Rieke B, Röbl-Mathieu M, Rosenbusch D, Schmidt-Chanasit J, Wichmann O, Wiedermann U, Zepp F, Burchard G: Recommendations of the Standing Committee on Vaccination (STIKO) and the German Society for Tropical Medicine, Travel Medicine and Global Health e. V. (DTG) on travel vaccination.V. (DTG) on travel vaccinations. Epid Bull 2023;14:1-193 | DOI: 1025646/112013. 2023.

WHO Expert Consultation on Rabies, third report. Geneva: World Health Organisation; 2018 (WHO Technical Report Series, No. 1012). Licence: CC BY-NC-SA 3.0 IGO.

Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, Meltzer MI, Dhankhar P, Vaidya SA, Jenkins SR, Sun B, Hull HF. Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunisation Practices. MMWR Recomm Rep. 2008;57(Rr-3):1-28.

Ross RS. Rabies prophylaxis: how to counsel in the family practice. MMW - Advances in Medicine. 2020;162(11):53-8.

Weißer K, Barth I, Keller-Stanislawski B. Safety of vaccines. Federal Health Gazette-Health Research-Health Protection. 2009;52(11):1053-64.

GlaxoSmithKline GmbH & Co KG (2019): Rabipur® Summary of Product Characteristics. Status November 2019. Available online at: https://portal.dimdi.de/amispb/doc/pei/Web/2613602-spcde-20191101.pdf (last accessed on: 11.08.2023)

Ravish HS, Sudarshan MK, Madhusudana SN, Annadani RR, Narayana DH, Belludi AY, et al. Assessing safety and immunogenicity of post-exposure prophylaxis following interchangeability of rabies vaccines in humans. Hum Vaccin Immunother. 2014;10(5):1354-8.

Tepsumethanon V, Lumlertdacha B, Mitmoonpitak C, Sitprija V, Meslin FX, Wilde H. Survival of naturally infected rabid dogs and cats. Clin Infect Dis. 2004;39(2):278-80.

Federal Ministry of Social Affairs, Health, Care and Consumer Protection (BMSGPK). Vaccinations for allergies. Version 2.0, 24.05.2022. Vienna: BMSGPK; 2022.

Sanofi. Verorab®. Information for healthcare professionals. 2024 [03.06.2024]. Available online at: https://mein.sanofi.de/produkte/verorab (last accessed on: 04/06/2024).