TYPHOID VACCINES

Typhoid fever is caused by the enteric bacterium Salmonella typhi. Active immunization against typhoid fever has been achieved with some success by vaccines. The various vaccines that have been employed over the years to prevent typhoid fever can be divided into five broad groups. 

      1. Inactivated whole cell parenteral vaccine
      2. Subunit parenteral vaccine
      3. Inactivated whole cell oral vaccine
      4. Polysaccharide -carrier protein conjugate parenteral vaccine
      5. Live attenuated oral vaccine

Inactivated whole cell parenteral vaccines: 
      1. Heat inactivated phenol preserved vaccine (TAB vaccine): Prepared by heating S.typhi, S.paratyphi A and S.paratyphi B cultures at 56^oC for one hour and then suspending in 0.5% phenol solution. This vaccine contains 1000 million bacteria per ml of S.typhi and 750 million bacteria per ml each of S.paratyphi A and S.paratyphi B. Primary immunization with this parenteral vaccine consists of two doses given four weeks apart with a single booster dose recommended every three years. 0.5 ml of vaccine is given in two subcutaneous doses at an interval of 4-6 weeks, which is followed by intradermal injection of 0.1 ml every three years. Subcutaneous injections can result in local reactions, which can be avoided by injecting 0.1ml intradermally. Certain countries use vaccines containing only inactivated S.typhi or a divalent vaccine consisting of S.typhi and S.paratyphi A cultures. In endemic areas vaccination is recommended for all children, in whom single dose might give sufficient protection, which may be maintained for several years by booster doses. This vaccine induces only humoral immunity but no local or cellular immunity. 
      2. Alcohol inactivated vaccine: It is superior to heat inactivated vaccine as Vi antigen is preserved.
      3. Acetone inactivated vaccine: The cultures are inactivates using acetone, then air dried or lyophilized. Vi antigens are preserved.
      4. Formalin inactivated phenol preserved vaccine: Cultures inactivated using formalin and vaccine is preserved using phenol.

Subunit parenteral vaccines:
Prepared using extracts or sonicates of S.typhi cultures. Various vaccines under this category are:
      1. Freeze-thaw extract vaccine
      2. Trypsinized extract vaccine
      3. Purified lipopolysaccharide vaccine prepared by hot water-phenol extraction method
      4. Purified Vi polysaccharide vaccine: This vaccine is composed of purified Vi polysaccharide from S.typhi (or Citrobacter freundii). Vi antigen is extracted from acetone-killed bacteria by using saline, ethanol and acetic acid or by treating with cetavlon. It is administered subcutaneously or intramuscularly as one dose of 25 µg to individuals under two years of age. Duration of protection is said to last for 3 years. To maintain protection, revaccination is recommended every three years. As with many other pure polysaccharide vaccines, no booster effect indicative of an immunological memory is observed. For this reason, protein-Vi polysaccharide conjugate vaccines are being developed.

Inactivated whole cell oral vaccine:
      1. Acetone inactivated vaccine
      2. Formalin inactivated vaccine

Live attenuated oral vaccine:
Ty21a is a live attenuated strain of S.typhi Ty21a that was developed in the early 1970s by chemical mutagenesis. It is a stable mutant (Gal E mutant) that lacks the enzyme UDP-galactose-4-epimerase. This mutant also lacks Vi antigen. On ingestion, it initiates an infection in the gut but does not multiply after 4-5 divisions. It is able to invade mononuclear cells but is not capable of intracellular survival. The vaccine is administered orally in the form of enteric-coated capsules in three-four doses given every other day on empty stomach with milk or water. Each dose contains approximately 2-4 x10⁹ cfu/ml. Duration of protection is said to last for 7 years. A booster dose may be given every five years. This vaccine is more immunogenic because it induces local immunity (sIgA) in the intestine. Because the vaccine contains living S.typhi organisms, it is contraindicated in patients who are immunosuppressed and in pregnancy. Cold chain must be ensued to maintain potency of vaccine.

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