ANTIRABIES VACCINE

Rabies is an invariably fatal infection of humans, acquired from the bite of an infected mammal. The reservoir includes dogs, wolves, foxes skunks, jackals and bats. There are estimated to be 75,000 cases of rabies each year worldwide. Rabies is fatal and there is no treatment after symptoms of the disease appear. However, the progression of rabies can be checked if immunization is started immediately after exposure (bite).

The immunization against rabies are of two types: Pre-exposure prophylaxis and Post-exposure prophylaxis
Types of anti-rabies vaccine:

1. Neural

   1. Pasteur's cord vaccine

   2. Fermi vaccine

   3. Semple vaccine

   4. Beta Propiolactone (BPL) vaccine

   5. Infant mouse brain vaccine

2. Non-neural

   1. Egg vaccines
      i. Duck egg vaccine (DEV)
      ii. Live attenuated chick embryo vaccine

   2. Tissue culture vaccine
      i. Human diploid cell vaccine (HDCV)
      ii. Purified chick embryo cell culture vaccine (PCECV)
      iii. Rabies vaccine Adsorbed (RAV)
      iv. Purified Vero cell rabies vaccine (PVRV)
      v. BHK - Rabies Vaccine

   3. Subunit vaccine

NEURAL VACCINES (NERVE TISSUE VACCINE):

• Pasteur's Cord Vaccine: Prepared by Louis Pasteur in 1885 by drying pieces of infected rabbit spinal cord over caustic potash for varying periods.

• Fermi Vaccine: Preparations of infected brain treated with phenol.

• Semple Vaccine: 5% suspension of sheep brain infected with fixed virus and inactivated with phenol at 37oC.

• Beta propiolactone (BPL) vaccine: Similar to semple vaccine, but the inactivating agent is beta propiolactone and supposed to be more antigenic.

• Infant mouse brain vaccine: Vaccine prepared from suckling mouse brain (scanty or absence of myelin in nerve tissue) and inactivated by UV irradiation, beta propiolactone or phenol.

Disadvantages of neural vaccines:
The major complication following neural vaccines is the post-vaccinal encephalitis. The myelin protein in the vaccine stimulates immune response, which in turn acts on the recipient's nervous system. Presence of residual live virus in some of the early preparations due to insufficient inactivation resulted in the disease itself. Infant mouse though has no or scanty myelin, occasional neurological complications have been noted.

NON-NEURAL VACCINES:

1. Egg Based Vaccines:

   • Duck Egg Vaccine: Vaccine prepared from fixed virus inactivated by beta propiolactone after adapting the virus to grow in specific pathogen-free (SPF) duck eggs. Limitation: Poor immunogenicity

   • Live Attenuated Chick Embryo Vaccine: Viruses attenuated by serial passage through eggs. Suitable for immunization of pet animals. Low Egg Passage vaccine (40-50 egg passage) for immunization of dogs of three months or more. High Egg Passage (HEP) vaccine (180 egg passage) for immunization of cattle and cats. Limitation: Suitable for animal immunization, risk of residual live virus

2. Tissue Culture Vaccine:

   • Human Diploid Cell Vaccine (HDCV): Vaccine developed in 1964 by growing fixed virus (Wistar's Pitman-Moore strain) on human diploid cell (WI-38 or MRC-5) and inactivated with beta propiolactone.

   • Purified Chick Embryo Cell Culture Vaccine (PCECV): Flury LEP strain grown on chick embryo cell culture and inactivated by beta propiolactone. (Marketed as Rabipur)

   • Rabies Vaccine, Adsorbed (RVA): The vaccine is prepared from the Kissling strain of rabies virus adapted to a diploid cell line of the fetal rhesus lung. The virus is inactivated with beta-propiolactone and concentrated by adsorption to aluminum phosphate.

   • Vero Cell Vaccine (VRV): Viruses are grown in vero cells and inactivated by formaldehyde. The inactivated poliomyelitis vaccine obtained from Vero cells, required a purification step in order to remove the residual cellular DNA, hence is known as the purified Vero cell rabies vaccines (PVRV).

   • BHK-Rabies Vaccine: Rabies virus strain L. Pasteur (Vero cell adapted) grown on BHK-21 C13 cell monolayers, inactivated with beta-propiolactone and adsorbed on Aluminum phosphate. (Still in trial stage)

3. Subunit (Recombinant) Vaccine: Recently developed recombinant vaccinia virus / G protein vaccine is being used to eradicate rabies in foxes in Europe.

Dosage of Vaccine (HDCV/ARV): The potency of tissue culture or duck-embryo derived vaccines must have a potency of at least 2.5IU per dose.

Intramuscular route (1ml/dose):
� Pre-exposure: Prophylaxis consists of three doses of rabies vaccine given on days 0, 7, and 21 or 28.
� Post-exposure (in non-immunized individuals): Consists of five doses given on days 0, 3, 7,14, and 28.
� Post-exposure (in immunized individuals): Consists of only two doses, days 0 and 3

For effective and early antibody response in those individuals who did not receive rabies immunoglobulin, the 2-1-1 multisite schedule may be followed. It consists of one intramuscular dose each given in right and left arm at day 0, followed by one dose in the deltoid muscle on days 7 and 21.

Intradermal route (0.1ml):
WHO recommends use of a intradermal regimen that consists of five 0.1ml doses given intradermally on two sites on days 2-2-2-0-1-1.

Dosage of Semple vaccine:
� For class I risk, a dose of 2 ml each given subcutaneously on the anterior abdominal wall for 7 days.
� For class II risk, a dose of 5 ml each given subcutaneously on the anterior abdominal wall for 14 days.
� For class III risk, a dose of 10 ml each given subcutaneously on the anterior abdominal wall for 14 days.
WHO does not recommend use of nerve-tissue derived vaccines.