groups when cases of disease occurs around 1 in 10,000 people.
Furthermore, multiple trial arms would be required to cover a
placebo control as well as other potential groups that would be
necessary depending on the vaccine being evaluated. This is further
complicated for vaccines in which a current standard of care exists
and cannot be ethically denied to patients. Consequently, the tested
vaccine needs a mechanism for demonstrating both superiority to
the current vaccine in certain tests while demonstrating
non-inferiority in areas of overlap. This situation is made more
complex by bacteria for which there are multiple strains or serotypes (e.g., Streptococcus pneumoniae) in which vaccines provide
protection against only a subset of bacterial diversity. If reduction
of disease were the only mechanism for evaluating efficacy, then not
only would new vaccines need to include sufficient patients to
statistically evaluate reduction of disease, this number would need
follow-up assays to demonstrate the vaccine’s efficacy in a serotypedependent manner.
Thus, numerous assays have been developed to link in vitro
assay results to clinical efficacy of vaccines. The quantitative power
of these assays, called “correlates of protection” (COPs), have been
demonstrated in a clinical setting to predict clinical utility of a
vaccine through in vitro testing. As a result, a vaccine’s efficacy
can be potentially determined using a number of patients that is
far lower than required using reduction in disease incidence.
One such COP for protein antigens against bacterial pathogens
is the development of assays that measure the production of antibodies against the bacteria. These may include enzyme-linked
immunosorbent assays (ELISAs) or neutralization assays such as
opsonophagocytic activity (OPA) assays in which antibody titers
and their ability to promote opsonization of bacteria is determined.
For example, through clinical trials, such assays have been developed for pneumococcal disease that include ELISAs which can
show IgG concentrations >0.35 μg/mL and OPA assays showing
50% bacteriocidal activity when dilution is less than 1 in
8 [15]. Since each of these values have been associated with the
efficacy of pneumococcal glycoconjugate vaccines, subsequent vaccines against the bacteria are able to demonstrate efficacy by achieving each of these titers for both previous and new serotypes
included in vaccines. Similar assays have also been developed
against various other bacterial pathogens to measure vaccine efficacy without requiring additional massive clinical trials.
Immunology Overview for Vaccine Development
7
Furthermore, multiple trial arms would be required to cover a
placebo control as well as other potential groups that would be
necessary depending on the vaccine being evaluated. This is further
complicated for vaccines in which a current standard of care exists
and cannot be ethically denied to patients. Consequently, the tested
vaccine needs a mechanism for demonstrating both superiority to
the current vaccine in certain tests while demonstrating
non-inferiority in areas of overlap. This situation is made more
complex by bacteria for which there are multiple strains or serotypes (e.g., Streptococcus pneumoniae) in which vaccines provide
protection against only a subset of bacterial diversity. If reduction
of disease were the only mechanism for evaluating efficacy, then not
only would new vaccines need to include sufficient patients to
statistically evaluate reduction of disease, this number would need
follow-up assays to demonstrate the vaccine’s efficacy in a serotypedependent manner.
Thus, numerous assays have been developed to link in vitro
assay results to clinical efficacy of vaccines. The quantitative power
of these assays, called “correlates of protection” (COPs), have been
demonstrated in a clinical setting to predict clinical utility of a
vaccine through in vitro testing. As a result, a vaccine’s efficacy
can be potentially determined using a number of patients that is
far lower than required using reduction in disease incidence.
One such COP for protein antigens against bacterial pathogens
is the development of assays that measure the production of antibodies against the bacteria. These may include enzyme-linked
immunosorbent assays (ELISAs) or neutralization assays such as
opsonophagocytic activity (OPA) assays in which antibody titers
and their ability to promote opsonization of bacteria is determined.
For example, through clinical trials, such assays have been developed for pneumococcal disease that include ELISAs which can
show IgG concentrations >0.35 μg/mL and OPA assays showing
50% bacteriocidal activity when dilution is less than 1 in
8 [15]. Since each of these values have been associated with the
efficacy of pneumococcal glycoconjugate vaccines, subsequent vaccines against the bacteria are able to demonstrate efficacy by achieving each of these titers for both previous and new serotypes
included in vaccines. Similar assays have also been developed
against various other bacterial pathogens to measure vaccine efficacy without requiring additional massive clinical trials.
Immunology Overview for Vaccine Development
7