framework for future work which has provided a demonstration
that immunization with a weakened or inactivated pathogen could
be used to provide immunity towards the live version.
Despite the utility of various WPVs, advanced fermentation and
culturing techniques for growing the pathogens were not initially
developed. As such technology became more advanced, vaccines
that targeted toxic factors produced by the pathogens were increasingly developed. This approach facilitated the development of vaccines against the bacteria that cause diphtheria and tetanus. As the
appreciation for using components of pathogens in vaccines in
place of the whole pathogen grew, subunit vaccines containing
polysaccharides (e.g., Pneumovax 23
® ), proteins (e.g., Flublok
® ),
and glycoconjugates (e.g., Prevnar) became increasingly developed.
However, one distinct disadvantage associated with subunit vaccines is that they invoke a considerably weaker immune response
compared to killed or attenuated vaccines [7]. This observation led
to the development of vaccine components known as adjuvants,
which boost the immunogenicity of subunit vaccines. Although
aluminum salt (alum-based) adjuvants are the most commonly
used adjuvants, alternatives containing attenuated endotoxin (i.e.,
monophosphoryl lipid A) [8] and an emulsion-based system [9]
have been developed.
As increasingly diverse systems were developed for the assembly
of vaccines, increasing the scientific understanding of the immune
system became important for optimizing vaccine efficacy. For
example, understanding the mechanism by which various portions
of bacteria or viruses (i.e., antigens) illicit an immune response is an
important factor in vaccine design. Protein antigens are generally
recognized as thymus cell (T cell)-dependent antigens, whereas
polysaccharides are T cell-independent antigens [10]. Consequently, solutions of bacterial polysaccharides are poorly immunogenic in infants and do not create a long-lasting immunological
memory [10]. This led to the development of glycoconjugate
vaccines, which conjugate bacterial polysaccharides to carrier proteins to promote a T cell-dependent response against the polysaccharides and provide potent immunity in infants [10]. Such
vaccines have been utilized for vaccination of infants against Streptococcus pneumoniae to provide serotype-specific immunization that
has reduced the incidence of invasive pneumococcal disease by over
90% [11, 12]. Taken together, these examples have motivated a
higher understanding of how the immune response vaccines illicit
translates into clinical efficacy.
Immunology Overview for Vaccine Development
3
that immunization with a weakened or inactivated pathogen could
be used to provide immunity towards the live version.
Despite the utility of various WPVs, advanced fermentation and
culturing techniques for growing the pathogens were not initially
developed. As such technology became more advanced, vaccines
that targeted toxic factors produced by the pathogens were increasingly developed. This approach facilitated the development of vaccines against the bacteria that cause diphtheria and tetanus. As the
appreciation for using components of pathogens in vaccines in
place of the whole pathogen grew, subunit vaccines containing
polysaccharides (e.g., Pneumovax 23
® ), proteins (e.g., Flublok
® ),
and glycoconjugates (e.g., Prevnar) became increasingly developed.
However, one distinct disadvantage associated with subunit vaccines is that they invoke a considerably weaker immune response
compared to killed or attenuated vaccines [7]. This observation led
to the development of vaccine components known as adjuvants,
which boost the immunogenicity of subunit vaccines. Although
aluminum salt (alum-based) adjuvants are the most commonly
used adjuvants, alternatives containing attenuated endotoxin (i.e.,
monophosphoryl lipid A) [8] and an emulsion-based system [9]
have been developed.
As increasingly diverse systems were developed for the assembly
of vaccines, increasing the scientific understanding of the immune
system became important for optimizing vaccine efficacy. For
example, understanding the mechanism by which various portions
of bacteria or viruses (i.e., antigens) illicit an immune response is an
important factor in vaccine design. Protein antigens are generally
recognized as thymus cell (T cell)-dependent antigens, whereas
polysaccharides are T cell-independent antigens [10]. Consequently, solutions of bacterial polysaccharides are poorly immunogenic in infants and do not create a long-lasting immunological
memory [10]. This led to the development of glycoconjugate
vaccines, which conjugate bacterial polysaccharides to carrier proteins to promote a T cell-dependent response against the polysaccharides and provide potent immunity in infants [10]. Such
vaccines have been utilized for vaccination of infants against Streptococcus pneumoniae to provide serotype-specific immunization that
has reduced the incidence of invasive pneumococcal disease by over
90% [11, 12]. Taken together, these examples have motivated a
higher understanding of how the immune response vaccines illicit
translates into clinical efficacy.
Immunology Overview for Vaccine Development
3