Rabies vaccine

Rabies vaccine are a prescription medication in the vaccine class.

The rabies vaccine has been approved to prevent transmission of the rabies virus, a viral infection spread by animal bites or scratches that can be lethal if not promptly treated.

It is not a part of routine national immunisation programs.

The rabies vaccination is usually administered intramuscularly, absorbed into the bloodstream, and distributed to immune system sites such as lymph nodes. It stimulates the production of antibodies and is slowly eliminated as immunity develops.

The common side effects of Rabies vaccine include pain, tenderness, redness at the injection site, back/joint pain, headache, fatigue, and dizziness.

Rabies vaccines are available as a suspension for injection.

Rabies vaccines are available in many countries globally like India, Germany, the United States, the United Kingdom, South Africa, China, Russia, Philippines, France, Canada and Australia.

The rabies vaccine is the vaccine class that stimulates immunity by producing antibodies against rabies virus infection.

The procedure used for producing the rabies vaccine is highly controlled. In the beginning step, particular virus strains are cultured in initial chicken fibroblast cells. To help develop the virus, a synthetic cell culture medium is incorporated with human albumin, processed bovine gelatin (polgrline), and antibiotics. The virus is then inactivated using propiolactone to render it non-infectious. The vaccine is further processed using zonal centrifugation on a sucrose density gradient to guarantee its purity and efficacy. Due to this process, the rabies vaccine has been proven safe, effective, and well-prepared to trigger the immune system when administered, providing significant protection against the rabies virus.

Rabies vaccines are available as a suspension for injection.

Suspension for injection: To be administered parenterally, as applicable.

Rabies vaccine is used to prevent rabies, a severe disease caused by the virus. It is commonly transmitted through the saliva of infected animals.

Rabies vaccine can help support the following health benefits:

• Prevention: Once symptoms develop, rabies, an infectious virus that attacks the central nervous system, is usually fatal. The potential of rabies vaccination to prevent this lethal illness in people is its primary benefit. The vaccine has the ability to neutralise the virus and stop it from advancing to symptomatic rabies when given quickly after a possible exposure, such as a bite from a rabid animal. For anyone who risks the danger of getting into contact with rabid animals, such as wildlife workers and veterinarians, this life-saving benefit proves particularly important.
• CommunityHealth: A community's risk of developing a rabies epidemic decreases through widespread rabies vaccination programmes for domestic animals like dogs and cats. The probability of rabies spreading throughout communities is decreased when household animals are immunised. This supports general public health and protects both human and animal populations.

• Post-Exposure Prophylaxis (PEP): Vaccinations against rabies are an essential element of post-exposure prophylaxis (PEP). This procedure involves administering the rabies vaccination to people who have been bitten, scratched, or in any other way come into contact with an animal that may be carrying the rabies virus. When started right away after exposure, PEP can be extremely successful in stopping the virus' progression and the development of rabies. Thus, rabies vaccination is promoting the health of the community.

• High-Risk Populations: Because they handle animals on a regular basis, several occupations put their workers at a higher risk of contracting rabies. People who work in these high-risk professions require rabies vaccination for its protection. Pre-exposure prophylaxis (PrEP) rabies vaccines are frequently given to professionals including veterinarians, animal control officers, and wildlife rehabbers to protect them from potential exposures while carrying out their jobs.

Rabies vaccines are approved for use in the following clinical indications:

• To help prevent rabies if an outbreak occurs, it is recommended that those at higher risk for rabies exposures, such as those who work with possibly infected animals, should get the vaccination.
• To prevent rabies transmission in people who have been bitten or scratched by possibly rabid animals, post-exposure prophylaxis requires rabies vaccination to induce immunity and prevent the onset of rabies after exposure.

Parenterally: Rabies vaccine is available in powder for injection. For children less than 2 years, the vaccine is injected into the anterolateral part of the thigh, whereas for children more than 2 years and adults, it is injected into the deltoid muscle. It should not be injected into the GLUTEAL MUSCLE-like buttock areas. It should be administered intramuscularly only and not intravenously, intradermally or subcutaneously.

It can be only given by a healthcare professional in a hospital setting as per a recommended schedule based on exposure risk assessment.

After administration, the healthcare provider will document the vaccination, including the date, time, dose, and injection site.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Rabies vaccine is available as a suspension for injection.

Suspension for injection: Freeze-dried suspension; ≥2.5 IU/mL

Dosage Adjustment for Adult Patients

• Preexposure Immunization

Vaccination is recommended for children residing in or visiting countries where exposure to rabid animals is a constant hazard should get vaccinated.

Primary dose:1 mL Intramuscularly x3 doses

Administer in series from days 0, 7, and 21 or 28

Booster: 1 mL intramuscularly to maintain a serum titer of more than 1:5 serum dilution by RFFIT

Frequency for testing serum titers

Continuous risk populations

Individuals who interact with live rabies virus in research laboratories and institutions that produce vaccines should have their blood checked for rabies antibodies every six months.

Frequent risk

Animal control and wildlife officers in places where rabies is enzootic, other laboratory workers (such as those providing rabies diagnostic tests), cavers, veterinarians and staff, and bat handlers, wherever they are, are also included.

Give a single booster dose of the vaccination if the titer is insufficient.

Infrequent risk

Those who have completed a full preexposure vaccination series with licenced vaccines and according to schedule, including veterinarians, veterinary students, terrestrial animal-control and wildlife officers, working in areas with low rabies endemicity, as well as some at-risk international travellers, do not need to receive routine preexposure booster doses of vaccine or routine booster serologic verification of detectable antibody titers.

• Rabies Postexposure Immunization

Unimmunized individuals

1 mL Intramuscularly x5 doses

Administer in series from days 0, 3, 7, 14, and 28 along with the administration of human rabies immune globulin (HRIG) on day 0 HRIG: 20 IU/kg; if anatomically possible, the full dose should be infiltrated all the way around and into the wound(s), and the remaining volume should be given intramuscularly (IM) at a site apart from the vaccination site.

Previously immunized individuals

1 mL intramuscularly 2 doses on days 0 and 3

Rabies vaccine is available as a suspension for injection.

Rabies vaccine should be used to prevent rabies infections, along with no appropriate dietary restrictions. Consuming regular foods and drinks before and after receiving the vaccine is safe.

However, staying fully hydrated and maintaining a balanced and healthy diet to support overall immune system function is always recommended, which can boost the effectiveness of vaccines.

The dietary restriction should be individualized as per patient requirements.

Rabies vaccine may be contraindicated in the following conditions: -

• Anaphylaxis reactions (Hypersensitivity to any component of the rabies vaccine)
• Guillain-Barré Syndrome (GBS)
• Concomitant use of anti-malarial medications
• Immunodeficiency disorders like HIV infection
• Severe previous response to the rabies vaccination

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Children with weak immune systems, such as those with HIV infection or cancer or who are taking certain drugs, may not respond as well to the rabies vaccine and may consult a healthcare professional who might suggest modifying the vaccine schedule or giving additional doses to these people to improve protection.
• It may be advisable to postpone the vaccination if the child is currently experiencing a fever or a moderate to severe sickness.
• Healthcare professionals should assess the risks and benefits of the vaccination in case of any severe allergic reactions or a severe reaction to a previous dose of the rabies vaccine.
• Rabies vaccines are not typically recommended during pregnancy unless there is a specific risk of rabies exposure.
• Use caution to avoid letting the vaccine into a blood vessel since there is a chance that it might cause shock. Aspirate carefully before injecting to ensure the needle is not in a vein.
• When administering the rabies vaccine simultaneously with rabies immunoglobulin or other vaccines, it is recommended to use separate syringes and distinct injection sites.

Safe to use during pregnancy.

There is no sufficient scientific evidence traceable regarding the use and safety of the Rabies vaccine in concurrent use with any particular food.

The adverse reactions related to Rabies vaccine can be categorized as

• Common: Pain, erythema, swelling or itching at the injection site, abdominal pain, headache, muscle aches and dizziness.
• Less Common: Serum sickness, fatigue and fever
• Rare: Severe allergic reactions

The clinically relevant drug interactions of the Rabies vaccine are briefly summarized here:

• Immunosuppressants- Drugs like prednisone or cyclosporine suppress the immune system and may reduce the effectiveness of Rabies vaccine.
• Antimalarial Medications: Drugs such as chloroquine may interfere with the immune response to the rabies vaccine and may reduce the effectiveness of the vaccine.
• Other Vaccines: Children are administered different vaccines to reduce any risk; it is generally recommended to administer them at separate sites and times from the rabies vaccine to minimize the risk of interference.

The common side of the Rabies vaccine includes the following-

• Redness, pain, swelling or tenderness where the shot was given
• Headache
• Joint pain
• Nausea
• Dizziness
• Fatigue
• Tiredness
• Headache
• Vomiting
• Diarrhea
• Chills
• Fever
• General feeling of discomfort or illness
• Stomach pain

The Rabies vaccine should be prudent in the following group of special populations.

• Pregnancy:

Rabies vaccines are usually considered safe during pregnancy; they are mainly advised when there is a significant risk of rabies exposure. Unless the risk of exposure is very high, routine vaccinations are usually not recommended during pregnancy.

• Paediatrics:

Dosage Adjustment for Paediatric Patients

• Preexposure Rabies Immunization

Vaccination is recommended for young children living in or visiting countries where exposure to rabid animals is a constant hazard should get vaccinated; according to statistics from all over the world, children are more at risk than adults.

Primary dose: 1 mL intramuscularly x3 doses

Administer in series from days 0, 7, and 21 or 28

Booster dose: 1 mL intramuscularly to maintain a serum titer of more than 1:5 serum dilution by RFFIT

• Rabies Postexposure Immunization

Unimmunized individuals

1 mL intramuscularly x5 doses

Administer in series from days 0, 3, 7, 14, and 28 along with the administration of human rabies immune globulin (HRIG) on day 0 HRIG: 20 IU/kg; if anatomically possible, the full dose should be infiltrated all the way around and into the wound(s), and the remaining volume should be given intramuscularly (IM) at a site apart from the vaccination site.

Previously immunized individuals

1 mL intramuscularly 2 doses on days 0 and 3

• Geriatrics:

There is no sufficient scientific evidence regarding the use and safety of the Rabies vaccine for geriatric populations.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of the Rabies vaccine for lactating mother populations.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdosage of Rabies vaccine rarely occurs as healthcare professionals administer it according to specific or precise dosing guidelines. Still, if it were to happen, it may include symptoms such as passing out or trouble breathing.

There is no specific antidote or treatment for excessive intake of rabies vaccine. Medical attention should be sought immediately when an overdose is suspected, followed by monitoring any adverse effects or allergic reactions. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Pharmacodynamics of Rabies vaccine:

Rabies vaccines have a physiological mechanism that plays a role in their pharmacodynamics. When the rabies vaccine is administered, the inactivated rabies virus antigens in the vaccine stimulate B cells to develop specific antibodies against the rabies virus after immunisation. When the virus is exposed, these antibodies in the bloodstream are destroyed. The rabies vaccination boosts the immune response by triggering the production of antibodies that are neutralising as well as the activation of T cells. Long-lasting defence is provided by the immunological memory cells. A vaccinated person's immune system can detect and fight the virus if exposed to rabies, which stops the disease from spreading. The effectiveness of the vaccination is to protect against rabies virus.

Pharmacokinetics of Rabies vaccine:

• Absorption: Rabies vaccine is administered intramuscularly, thus bypassing the absorption from the gastrointestinal tract. It is absorbed into the bloodstream from the injection site (the muscle tissue).
• Distribution: Antigens from the inactivated rabies virus, which are a vaccination component, circulate throughout the body and reach immune system sites such as lymph nodes.
• Metabolism: Rabies vaccines do not undergo significant metabolism in the body and function as antigens by developing antibodies resistant to the rabies virus.
• Elimination: As the immune response develops, the vaccine's components are gradually eliminated from blood circulation. This response results in the production of rabies-specific antibodies, which provide immunity against the virus.

Onset (antibodies): 7 to10 days

Duration (antibodies): More than 1 year

Peak Plasma Time (antibodies): 30 to 60 days

• Ertl, Hildegund C J. “New Rabies Vaccines for Use in Humans.” Vaccines vol. 7,2 54. 20 Jun. 2019, doi:10.3390/vaccines7020054
• Khalil, Walaa M et al. “Evaluation and Correlation of Rabies Vaccine Potency Using the National Institute of Health, Rapid Focus Fluorescent Inhibition, and Passive Hemagglutination Tests.” Viral immunology vol. 35,2 (2022): 159-169. doi:10.1089/vim.2021.0181
• McGettigan, James P. “Experimental rabies vaccines for humans.” Expert review of vaccines vol. 9,10 (2010): 1177-86. doi:10.1586/erv.10.105

• Inform the caregivers of the schedule for administering the rabies vaccine, whether for preexposure or post-exposure prophylaxis, ensuring the patient understands the timing and number of doses.
• Assure caregivers that rabies vaccine immunizations are generally safe, with only minor, short side effects. Encouraging them to immediately report any unexpected or severe responses to the healthcare physician and, whenever applicable, to use reporting systems like the Vaccine Adverse Event Reporting System (VAERS)
• Inform caregivers of the recommended immunization schedule, which usually consists of two or three doses, depending on the vaccine brand. Also, mention the ages at which the doses should be administered and give the Vaccine Information Statements, which must be disclosed before immunization by the National Childhood Vaccine Injury Act of 1986 about the Centres for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines), these resources are freely accessible.

• https://www.ncbi.nlm.nih.gov/books/NBK448076/
• https://www.indianpediatrics.net/oct2014/785 figure1.pdf
• https://www.cdc.gov/vaccines/hcp/vis/vis-statements/rabies.html
• https://medicalguidelines.msf.org/
• https://www.cdc.gov/vaccines/schedules/hcp/index.html