pathogens which encode antigens to stimulate immune response
are expressed in microbial cells. Varieties of expression systems are
available with a variety of advantages and produce the required
antigens in large quantities [76]. Using this approach many types
of vaccines have been developed such as Ty21a vaccine for typhoid,
CVD103-HgR cholera vaccine, cholera toxin B, human papilloma
virus (HPV) vaccine using L1 protein, hepatitis B virus, bivalent
oral vaccine for typhoid fever and cholera-related diarrhea, and
Salmonella enterica serovar Enteritidis antigens [77–79].
3 Whole-Cell Vaccines and Their Uses
The concept of whole-cell vaccines arrived more than 60 years ago.
According to a WHO report, the whole-cell vaccine design is based
on the strain selection, and it should be performed by knowing the
complete information about the characterization of the strain
[80]. The whole-cell vaccine can be cultured in various seed lot
systems; different media are also available, but synthetic media are
preferentially used for production purposes [81] as it is found that
synthetic media have defined components suitable for specific
microbial growth. In addition, there is a very low chance of contamination of other types of microbes in synthetic media. In
designing whole-cell vaccines, the inactivation of the toxin is an
important factor, and it can be done by different methods such as
chemical treatment, acid treatment, and radiation [82]. The final
product must be analyzed to check that no heat-labile toxins are
present in it. WHO has developed the guidelines for quality control, standardization, and production of whole-cell vaccines. For
example, strains of B. pertussis used in vaccine production should be
well characterized and as more components than just the strain are
used in vaccines preparation, the bacterial content before detoxification and killing must be determined by comparison with 10 IU of
WHO opacity standard. The concentration of bacteria in a single
human vaccine dose should not be more than 20 IU and not less
than 4.0 IU with a lower limit of the estimated potency not less
than 2.0 IU. The storage of whole-cell vaccines should be done at
2–8
C [83, 84]. The intracerebral mouse protection test (Kendrick
test) is also considered an effective assay to analyze the potency of
whole-cell pertussis vaccines and it is also assumed that this is the
only test showing a correlation with protection in children
[85, 86]. It has been reported that whole-cell vaccines can functionally be used in infants and toddlers in several countries for a
long duration of periods depending on dose and the immune
reaction of individuals. Bacterial cell components must also be
analyzed for virulence and immunogenicity while designing the
whole-cell vaccines.
Whole-Cell Vaccine Preparation: Options and Perspectives
255
are expressed in microbial cells. Varieties of expression systems are
available with a variety of advantages and produce the required
antigens in large quantities [76]. Using this approach many types
of vaccines have been developed such as Ty21a vaccine for typhoid,
CVD103-HgR cholera vaccine, cholera toxin B, human papilloma
virus (HPV) vaccine using L1 protein, hepatitis B virus, bivalent
oral vaccine for typhoid fever and cholera-related diarrhea, and
Salmonella enterica serovar Enteritidis antigens [77–79].
3 Whole-Cell Vaccines and Their Uses
The concept of whole-cell vaccines arrived more than 60 years ago.
According to a WHO report, the whole-cell vaccine design is based
on the strain selection, and it should be performed by knowing the
complete information about the characterization of the strain
[80]. The whole-cell vaccine can be cultured in various seed lot
systems; different media are also available, but synthetic media are
preferentially used for production purposes [81] as it is found that
synthetic media have defined components suitable for specific
microbial growth. In addition, there is a very low chance of contamination of other types of microbes in synthetic media. In
designing whole-cell vaccines, the inactivation of the toxin is an
important factor, and it can be done by different methods such as
chemical treatment, acid treatment, and radiation [82]. The final
product must be analyzed to check that no heat-labile toxins are
present in it. WHO has developed the guidelines for quality control, standardization, and production of whole-cell vaccines. For
example, strains of B. pertussis used in vaccine production should be
well characterized and as more components than just the strain are
used in vaccines preparation, the bacterial content before detoxification and killing must be determined by comparison with 10 IU of
WHO opacity standard. The concentration of bacteria in a single
human vaccine dose should not be more than 20 IU and not less
than 4.0 IU with a lower limit of the estimated potency not less
than 2.0 IU. The storage of whole-cell vaccines should be done at
2–8
C [83, 84]. The intracerebral mouse protection test (Kendrick
test) is also considered an effective assay to analyze the potency of
whole-cell pertussis vaccines and it is also assumed that this is the
only test showing a correlation with protection in children
[85, 86]. It has been reported that whole-cell vaccines can functionally be used in infants and toddlers in several countries for a
long duration of periods depending on dose and the immune
reaction of individuals. Bacterial cell components must also be
analyzed for virulence and immunogenicity while designing the
whole-cell vaccines.
Whole-Cell Vaccine Preparation: Options and Perspectives
255