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types: Inaba and Ogawa. A 1.0 ml typical dose usually contains not less than 8 billion V. cholerae particles and phenol (up to 0.5%) may be added as preservative. The vaccine can also be prepared in freeze-dried form. When stored refrigerated, the liquid vaccine displays a usual shelf-life of 18 months, while that of the dried product is 5 years.
Attenuated and inactivated viral vaccines
Viral particles destined for use as vaccines are generally propagated in a suitable animal cell culture system. While true cell culture systems are sometimes employed, many viral particles are grown in fertilized eggs, or cultures of chick embryo tissue (Table 10.13).
Many of the more prominent vaccine preparations in current medical use consist of attenuated viral particles (Table 10.11). Mumps vaccine consists of live attenuated strains of Paramyxovirus parotitidis. In many world regions, it is used to routinely vaccinate children, often a part of a combined measles, mumps and rubella (MMR) vaccine. Several attenuated strains have been developed for use in vaccine preparations. The most commonly used is the Jeryl Linn strain of the mumps vaccine, which is propagated in chick embryo cell culture. This vaccine has been administered to well over 50 million people worldwide and, typically, results in seroconversion rates of over 97%. The Sabin (oral poliomyelitis) vaccine consists of an aqueous suspension of poliomyelitis virus, usually grown in cultures of monkey kidney tissue. It contains approximately 1 million particles of poliomyelitis strains 1, 2 or 3 or a combination of all three strains.
Hepatitis A vaccine exemplifies vaccine preparations containing inactivated viral particles. It consists of a formaldehyde-inactivated preparation of the HM 175 strain of hepatitis A virus. Viral particles are normally propagated initially in human fibroblasts.
Table 10.13. Some cell culture systems in which viral particles destined for use as viral vaccines are propagated
Viral particle/vaccine Typical cell culture system
Yellow fever virus Chick egg embryos
Measles virus (attenuated) Chick egg embryo cells
Mumps virus (attenuated) Chick egg embryo cells
Polio virus (live, oral, i.e. Sabin and inactivated Monkey kidney tissue culture
injectable, i.e. Salk)
Rubella vaccine Duck embryo tissue culture, human tissue culture
Hepatitis A viral vaccine Human diploid fibroblasts
Varicella-zoster vaccines (chicken pox vaccine) Human diploid cells
Table 10.14. Some vaccine preparations that consist not of intact attenuated/inactivated pathogens but of surface antigens derived from such pathogens
Vaccine Specific antigen used
Anthrax vaccines Antigen found in the sterile filtrate of Bacillus anthracis
Haemophilus influenzae Purified capsular polysaccharide of Haemophilus influenzae type B
Hepatitis B vaccines Hepatitis B surface antigen (HBsAg) purified from plasma of hepatitis
Meningococcal vaccines Purified (surface) polysaccharides from Neisseria meningitidis (groups
A or C)
Pneumococcal vaccine Purified polysaccharide capsular antigen from up to 23 serotypes of
Toxoids, antigen-based and other vaccine preparations
Diphtheria and tetanus vaccine are two commonly used toxoid-based vaccine preparations. The initial stages of diphtheria vaccine production entails the growth of Corynebacterium diphtheriae. The toxoid is then prepared by treating the active toxin produced with formaldehyde. The product is normally sold as a sterile aqueous preparation. Tetanus vaccine production follows a similar approach; Clostridium tetani is cultured in appropriate media, the toxin is recovered and inactivated by formaldehyde treatment. Again, it is usually marketed as a sterile aqueous-based product.
Traditional antigen-based vaccine preparations consist of appropriate antigenic portions of the pathogen (usually surface-derived antigens; Table 10.14). In most cases, the antigenic substances are surface polysaccharides. Many carbohydrate-based substances are inherently less immunogenic than protein-based material. Poor immunological responses are thus often associated with administration of carbohydrate polymers to humans, particularly to infants. The antigenicity of these substances can be improved by chemically coupling (conjugating) them to a protein-based antigen. Several conjugated Haemophilus influenzae vaccine variants are available. In these cases, the Haemophilus capsular polysaccharide is conjugated variously to diphtheria toxoid, tetanus toxoid or an outer membrane protein of Neisseria meningitidis (group B).