Viral Vaccines

VIRAL VACCINES

Poliomyelitis

The virus (type 1, 2, 3) is grown in monkey kidney cell culture and two vaccines are prepared from it.

Oral Poliovirus Vaccine (OPV; Sabin Vaccine)

It is the live virus available in 10 ml and 50 ml vials; each dose is 2 drops, dropped directly in the mouth. The virus multiplies in the intestines and produces active immunity, simulating natural infection, without producing symptoms of the disease. For primary immunization OPV is now generally given at birth and then at 6, 10 and 14 weeks. Booster doses are given between 15–18 months and at school entry. OPV is the vaccine of choice for active immunization of children because it is simple to administer, is well accepted, induces systemic as well as intestinal immunity (the portal of entry of disease virus) and is highly efficacious. The intestinal immunity also eliminates carrier state and thus limits spread of the disease. It is advised to postpone the vaccine in presence of vomiting and diarrhoea. Vaccine associated paralysis occurs extremely rarely.

Simultaneous vaccination of all infants and children upto 5 years age (pulse polio programme) has eradicated the wild virus in many countries by colonizing all susceptible intestines by the vaccine virus. This programme is underway in India.

Inactivated Poliomyelitis Vaccine (IPV, Salk Vaccine)

It is inactivated suspension of the virus which is preferred over OPV only for:

primary immunization in adults (risk of vaccine associated paralysis following OPV is higher in adults).  In persons with compromized immune system. Three doses of 1 ml each are injected s.c. in the deltoid region at 4–6 week intervals and a fourth is given 6–12 months later. Booster doses are given every 5 years. Fever and local pain are common. Allergic reactions sometimes occur, probably to the animal protein present in the vaccine.

Rabies

Four rabies vaccines have been produced.

Antirabic Vaccine Carbolized (Semple Vaccine)

Also called ‘Neural tissue vaccine’ (NTV), it is a 5% suspension of sheep brain substance containing carbolic acid fixed rabies virus. Though long considered obsolete because of poorer efficacy, need for 14 daily painful large volume (2–5 ml) injections into the anterior abdominal wall, and risk of serious (even fatal) vaccine associated allergic encephalomyelitis, it continued to be used in Government hospitals in India till mid 2005, after which it has been discontinued.

Purified Chick Embryo Cell Vaccine (PCEV)

It consists of FluryLEP strain of rabies virus grown on chick fibroblasts and inactivated by βpropiolactone; available as 2.5 IU in 1 ml amp (RABIPUR). The efficacy of this vaccine is nearly equal to HDCV, and it produces local reactions in ~5% cases. However, rare neuroparalytic complications have been reported. Local pain, erythema, swelling and lymph node enlargement can occur.

Human Diploid Cell Vaccine (HDCV)

It is lyophilized inactivated rabies virus grown in human diploid cell culture. The vial containing 2.5 IU is freshly suspended in 1 ml of diluent.

A local reaction—redness and slight induration lasting 1–2 days occurs in 10% cases. Fever and arthralgia is reported in 1%. HDCV is ~100% effective and well tolerated. Vaccine associated encephalitis does not occur.

Purified Vero Cell Rabies Vaccine (PVRV)

This contains inactivated wistar rabies PM/WI3815033M strain grown on vero continuous cell line

(VERORAB 1 ml; VEROVAXR 0.5 ml).

Post-exposure prophylaxis: This is given to all non-immunised animal bite cases suspected to have been exposed to the rabies virus. The intradermal (i.d.) regimen for all tissue culture rabies vaccines called the ‘Thai regimen’ that has been recommended by the WHO since 1992, has only recently (in 2006) been approved and notified by the Government of India. This regimen requires only 1/5 dose of the earlier used i.m. regimen, is less expensive, more convenient and equally efficacious. In this regimen 0.1 ml of PCEV or PVRV or 0.2 ml of HDCV is injected i.d. at 2 sites (over deltoid of both arms) on days 0, 3 and 7 followed by 1 site injection on day 28 (or 30) and day 90, (2 + 2 + 2 + 1 + 1 = 8 injections). Thus, no injection is given on day 14 as in earlier i.m. regimen which employed 1 ml PCEV/HDCV or 0.5 ml PVRV per injection on days 0, 3, 7, 14, 30, 90.

Because rabies vaccines take 10–14 days to develop protective antibodies, concurrent administration of rabies immunoglobulin (RIG) is recommended in category III bites, where risk of contacting rabies is high.

An alternative 8 site i.d. regimen (Oxford regimen) is advocated for an earlier antibody response, particularly when RIG is not available for postexposure treatment. In this regimen 0.1 ml of PCEV or HDCV (but not PVRV) is injected at 8 sites (over both deltoids, suprascapular region, thighs and abdomen) on day 0. On 7th day 4 sites are injected followed by one site injection on day 28 and 90 (total 14 injections).

Pre-exposure prophylaxis (Primary vaccination): This is usually recommended for veterinary workers and animal handlers, who are at high risk of animal bites. Three i.d. injections of 0.1 ml each of PCEV/HDCV/PVRV are given on days 0, 7 and 28. Booster doses are recommended every 2 years so long as the person remains at risk.

Post-exposure prophylaxis in already vaccinated subjects: This is given when an immunized person is bitten by a suspected animal. Three 0.1 ml i.d. injections are given on days 0, 3 and 7.

Local treatment of bite wound: Early local treatment of bite wound is essential in addition to the vaccine ± RIG. The wound should be thoroughly washed with soap under running water for at least 5 min, followed by application of an antiseptic (alcohol/povidone iodine/cetrimide). Cauterization with carbolic acid is contraindicated. In category III bites, RIG should be infiltrated locally in the depth and around the wound to inactivate the locally present virus. Suturing of the wound should be avoided, at least for 2 days.

Influenza Virus Vaccine

Contains inactivated influenza virus A and B. Immunization may be done annually or during an epidemic: 2 injections of 0.5–1 ml i.m. 1–2 months apart. Influenza virus undergoes frequent antigenic changes; hence the efficacy of the vaccine is inconsistent. It is indicated only in high risk cases.

Adverse reactions are commoner in children —local tenderness and induration occurs in 30%. Fever, malaise and myalgia lasting 1–2 days is less frequent. Allergic reactions to the egg protein present in the vaccine occur rarely.

Hepatitis B Vaccine

The new hepatitis B vaccine (ENGERIXB) is prepared in yeast cells by recombinant DNA technique and contains aluminium hydroxide adsorbed hepatitis B virus surface antigen 20 μg in 1 ml suspension. Three 1 ml injections in the deltoid muscle given at 0, 1 and 6 months produce protective antibody titers in 99% subjects. Children <10 yr are given 0.5 ml doses in the thigh. Now included in universal immunization for all, but is especially indicated in persons who come in contact with blood, blood products and other body fluids (surgeons, dentists, blood bank personnel, laboratory technicians and other health care workers, haemophilics, haemodialysis patients, drug addicts, etc). Induration and soreness at injection site and occasional fever and malaise are the adverse effects.

Hepatitis A Vaccine

It is prepared by inactivating with formaldehyde hepatitis A virus grown in human diploid cell culture. A single 0.5 ml i.m. injection in deltoid muscle affords protection, but a booster dose after 6 month is recommended.

AVAXIM 0.5 ml prefilled syringe, HAVRIX 0.5 ml inj.

Mumps Virus Vaccine Live Attenuated

It is prepared from mumps virus grown in cell culture of chick embryo. A single dose of 5000 TCID₅₀ (tissue culture infectious dose 50%) affords protection for 10 years; revaccination is not required. Clinical disease may occur if the vaccine is given after exposure to natural mumps. It is generally combined with measles and rubella vaccine (MMR), and is not recommended below 1 year of age. A mild febrile reaction occurs occasionally.

Measles Vaccine Live Attenuated

This is also a vaccine grown on chick embryo; available in single dose vials containing 1000 TCID₅₀ of Edmonston Schwarz strain (ROUVAX, RIMEVAX) or Edmonston zagreb strain (MVAC) for s.c. injection over right deltoid region. It produces a modified infection—fever, rash and coryza may appear after 5–10 days; immunity lasts 8 years and no booster doses are required. It is recommended in children 9 months or older. Ordinarily, adults need not be immunized. Malnourished, chronically ill and tuberculous children must be protected to minimize the risk of serious complications of natural measles. Some protection is afforded even if given after exposure. It should be given with caution to children with history of febrile convulsions or parental history of epilepsy.

Rubella Vaccine (RVAC)

It contains live attenuated rubella virus Wistar RA27/3 strain 1000 TCID₅₀ per 0.5 ml inj. for deep s.c. or i.m. injection in upper arm. It is used especially in girls from 1 yr age to puberty—for immunization against German measles; mostly as combined MMR vaccine. It is contraindicated during pregnancy, febrile illness and in untreated tuberculosis patients. Reactions are fever, malaise, sore throat, joint pain and lymphadenopathy.

Measles Mumps Rubella (MMR) Vaccine

Two preparations of this combined live vaccine are available: have similar efficacy.

TRIMOVAX lyophilized measles 1000 TCID₅₀ of Schwarz strain, mumps 5000 TCID₅₀ and rubella 1000 TCID₅₀ per unit dose (0.5 ml) vial.

TRESIVAC lyophilized measles 5000 TCID₅₀ of Edmonston Zagreb strain, mumps 5000 TCID₅₀ and rubella 4000 TCID₅₀ per unit dose (0.5 ml) vial.

A single dose injected s.c. over right deltoid is indicated in children older than 12 months for protection against these 3 diseases. Mild fever, rash, enlargement of cervical/occipital lymph nodes and parotid glands and local induration may occur after ~5 days. It is absolutely contraindicated during pregnancy; adult female vaccinees should not conceive for at least 2 months.

Varicella Vaccine

It is lyophilised live attenuated OKa strain of varicellazoster virus grown in human diploid cell culture, containing 103.3 PFU (plaque forming units) of the virus. A single dose induces antibody response in > 98% children and affords protection for 10 years.

Dose: 0.5 ml s.c. single dose for children 1–12 years, and 2 doses 6–10 weeks apart in those > 12 years.

VRILRIX, OKAVAX 0.5 ml inj.

Contraindicated during pregnancy, in those with lymphocytopenia and within 1 month of measles vaccination. Mild local reaction, papular eruption and shortlasting fever occurs in 4–5% children.