chronic infections like HIV are more challenging due to safety and
efficacy concerns [42]. This process had been used by Pasteur and
his colleagues to develop vaccines against the diarrheal diseasecausing agent in chickens, that is, Pasteurella multocida [36], animal poxvirus (probably horsepox) against smallpox [43], bovine
tuberculosis bacteria against human tuberculosis [44, 45]. The
development of vaccines for measles, mumps, oral polio, rubella,
tetravalent dengue, and varicella was made by an in vitro selection
of clones by cell-culture passage [42]. The principle behind the
development of live, attenuated viral vaccines is that its virulence
may be sufficiently attenuated by successively subculturing while
retaining the required antigens to induce immune responses. It is
also suggested that passage in cell culture causes cells to grow in the
culture medium, and the mutants will grow comprising modified
harmful genes that control the infection of the organism in the host
[36]. This method enabled the selection and isolation of mutants
for the oral polio vaccine, which was not able to cause paralysis.
These mutations were at least moderately lost during the growth of
attenuated cells in the human intestine, and this causes infrequent
incidences of postvaccination paralysis [46].
Inactivation is an important method for vaccine development.
These are also recognized as killed whole-cell vaccines. Inactivation
of the agent is done by heat treatment, chemical treatment, formalin treatment, β-propiolactone treatment, and so on so that infectivity of the agent is eliminated and it loses its ability to replicate,
but its immunogenicity is retained [36, 47]. These vaccines generally offer a shorter duration of protection and thus require booster
doses for long-term immunity [41]. This method has been used to
develop a large number of vaccines such as vaccines for cholera,
plague, typhoid, pertussis, polio, hepatitis A, influenza, and yellow
fever vaccine [47–49].
Reassortment is recognized as a key evolutionary mechanism
present in segmented RNA viruses [50]. This mechanism enables
the development of virus having RNA segments of two viruses by
cocultivation of two viruses. This method has enabled the development of live and inactivated influenza and rotavirus vaccines [51].
Encapsulated bacteria cause diseases among infants, the elderly,
and immunocompromised persons. It was observed that antibodies
against the polysaccharide capsule increased phagocytosis, and this
property led to the development of capsular polysaccharide vaccines. The immune response triggered by polysaccharide antigens
protects against encapsulated bacteria. Polysaccharide vaccines have
been reported against Neisseria meningitidis, Salmonella typhi, and
Streptococcus pneumoniae. Capsular polysaccharides for vaccine preparations have been reported for the development of the meningococcal polysaccharide vaccine [30, 52, 53], pneumococcal
polysaccharides vaccines [54], and Haemophilus influenzae type b
capsular vaccine [55]. It was also found that such vaccines
Whole-Cell Vaccine Preparation: Options and Perspectives
253
efficacy concerns [42]. This process had been used by Pasteur and
his colleagues to develop vaccines against the diarrheal diseasecausing agent in chickens, that is, Pasteurella multocida [36], animal poxvirus (probably horsepox) against smallpox [43], bovine
tuberculosis bacteria against human tuberculosis [44, 45]. The
development of vaccines for measles, mumps, oral polio, rubella,
tetravalent dengue, and varicella was made by an in vitro selection
of clones by cell-culture passage [42]. The principle behind the
development of live, attenuated viral vaccines is that its virulence
may be sufficiently attenuated by successively subculturing while
retaining the required antigens to induce immune responses. It is
also suggested that passage in cell culture causes cells to grow in the
culture medium, and the mutants will grow comprising modified
harmful genes that control the infection of the organism in the host
[36]. This method enabled the selection and isolation of mutants
for the oral polio vaccine, which was not able to cause paralysis.
These mutations were at least moderately lost during the growth of
attenuated cells in the human intestine, and this causes infrequent
incidences of postvaccination paralysis [46].
Inactivation is an important method for vaccine development.
These are also recognized as killed whole-cell vaccines. Inactivation
of the agent is done by heat treatment, chemical treatment, formalin treatment, β-propiolactone treatment, and so on so that infectivity of the agent is eliminated and it loses its ability to replicate,
but its immunogenicity is retained [36, 47]. These vaccines generally offer a shorter duration of protection and thus require booster
doses for long-term immunity [41]. This method has been used to
develop a large number of vaccines such as vaccines for cholera,
plague, typhoid, pertussis, polio, hepatitis A, influenza, and yellow
fever vaccine [47–49].
Reassortment is recognized as a key evolutionary mechanism
present in segmented RNA viruses [50]. This mechanism enables
the development of virus having RNA segments of two viruses by
cocultivation of two viruses. This method has enabled the development of live and inactivated influenza and rotavirus vaccines [51].
Encapsulated bacteria cause diseases among infants, the elderly,
and immunocompromised persons. It was observed that antibodies
against the polysaccharide capsule increased phagocytosis, and this
property led to the development of capsular polysaccharide vaccines. The immune response triggered by polysaccharide antigens
protects against encapsulated bacteria. Polysaccharide vaccines have
been reported against Neisseria meningitidis, Salmonella typhi, and
Streptococcus pneumoniae. Capsular polysaccharides for vaccine preparations have been reported for the development of the meningococcal polysaccharide vaccine [30, 52, 53], pneumococcal
polysaccharides vaccines [54], and Haemophilus influenzae type b
capsular vaccine [55]. It was also found that such vaccines
Whole-Cell Vaccine Preparation: Options and Perspectives
253