dependent antigen, the surface protein, was able to provide an
immune response similar to that observed for direct chemical conjugation of polysaccharides to carrier proteins (i.e., glycoconjugate
vaccines). Furthermore, the researchers demonstrated that the
resulting immune response provides protection against pneumococcal disease using various animal models and an in vitro correlate
assay [13, 14]. This work highlights how a vaccine was designed to
invoke a specific immune response to provide protection against
pneumococcal infections.
As an alternative to the aforementioned immune response, the
immune system can direct a response towards infected bodily cells.
This occurs through the action of CD8+ T cells that recognize
peptides (processed antigen fragments produced intracellularly)
attached to the surface of cells via the MHC I receptor (Fig. 1).
Unlike MHC II, which is present on APCs, MHC I is expressed on
the surface of nucleated bodily cells. If a cell becomes infected with
a virus or becomes a tumor, intracellular proteins can be processed
for presentation on the cellular surface via attachment to MHC I
and then be recognized by CD8+ T cells. When the T cells recognize and bind to the epitope-bound MHC I receptor, the T cell
becomes activated and can initiate a cellular immune response. In
this response, the T cell secretes cytokines, such as tumor necrosis
factor alpha (TNFα) or interferon gamma (IFN-γ), that demonstrate antitumor and antiviral effects. The T cells also secrete cytotoxic chemicals that serve to create pores within the membrane of
the bound cells through which proteases can enter. Once the
proteases have entered the targeted cell, they are able to degrade
any viral proteins and promote cellular apoptosis. Once this has
been achieved, the CD8+ T cell is able to continue its response as
needed against additional infected cells.
3 Development of Assays to Evaluate Vaccine Efficacy
In order to determine whether a vaccine has the potential to
provide protective immunity within a patient, various assays have
been developed to evaluate the immune response and determine
whether it is sufficiently protective. One significant challenge facing
various vaccines is the fact that the incidence rate of disease is
frequently very low. As shown in Table 1, the incidence and fatality
rates of bacterial pathogens frequently occurs on the rate of a few
cases per hundred thousand people. Consequently, performance of
clinical trials to demonstrate efficacy of vaccines against these
organisms represents a substantial challenge since a massive number
of patients would be necessary. For example, if a clinical trial is
seeking to demonstrate the efficacy of the vaccine through the
reduction of disease incidence or associated death, a sufficient
number of patients would be required to capture differences of
6
Andrew Hill et al.
immune response similar to that observed for direct chemical conjugation of polysaccharides to carrier proteins (i.e., glycoconjugate
vaccines). Furthermore, the researchers demonstrated that the
resulting immune response provides protection against pneumococcal disease using various animal models and an in vitro correlate
assay [13, 14]. This work highlights how a vaccine was designed to
invoke a specific immune response to provide protection against
pneumococcal infections.
As an alternative to the aforementioned immune response, the
immune system can direct a response towards infected bodily cells.
This occurs through the action of CD8+ T cells that recognize
peptides (processed antigen fragments produced intracellularly)
attached to the surface of cells via the MHC I receptor (Fig. 1).
Unlike MHC II, which is present on APCs, MHC I is expressed on
the surface of nucleated bodily cells. If a cell becomes infected with
a virus or becomes a tumor, intracellular proteins can be processed
for presentation on the cellular surface via attachment to MHC I
and then be recognized by CD8+ T cells. When the T cells recognize and bind to the epitope-bound MHC I receptor, the T cell
becomes activated and can initiate a cellular immune response. In
this response, the T cell secretes cytokines, such as tumor necrosis
factor alpha (TNFα) or interferon gamma (IFN-γ), that demonstrate antitumor and antiviral effects. The T cells also secrete cytotoxic chemicals that serve to create pores within the membrane of
the bound cells through which proteases can enter. Once the
proteases have entered the targeted cell, they are able to degrade
any viral proteins and promote cellular apoptosis. Once this has
been achieved, the CD8+ T cell is able to continue its response as
needed against additional infected cells.
3 Development of Assays to Evaluate Vaccine Efficacy
In order to determine whether a vaccine has the potential to
provide protective immunity within a patient, various assays have
been developed to evaluate the immune response and determine
whether it is sufficiently protective. One significant challenge facing
various vaccines is the fact that the incidence rate of disease is
frequently very low. As shown in Table 1, the incidence and fatality
rates of bacterial pathogens frequently occurs on the rate of a few
cases per hundred thousand people. Consequently, performance of
clinical trials to demonstrate efficacy of vaccines against these
organisms represents a substantial challenge since a massive number
of patients would be necessary. For example, if a clinical trial is
seeking to demonstrate the efficacy of the vaccine through the
reduction of disease incidence or associated death, a sufficient
number of patients would be required to capture differences of
6
Andrew Hill et al.