has resulted in a change in societal and individual perspectives on the overall risk-to-benefit assessment for OPV in the United States (Plotkin, 1995). The availability of two complementary vaccines for the same disease allowed for a change in national recommendations in 1996: eIPV is now recommended for at least the first two of the four polio immunizations in the United States. This policy assures the protection of the population against natural infection of those immunized against the rare but real possibility of adverse effects of vaccination.
As the polio success story demonstrates, active vaccine development efforts in the face of changing epidemiology, scientific advances in basic virology, licensure of more than one polio vaccine, improvements in existing polio vaccines, worldwide efforts at eradication, and re-evaluation of domestic vaccination policies have all been necessary to give the U.S. population nearly complete protection from the threat of polio virus at the close of the 20th century.
As illustrated in the previous section, rapid scientific advances, changes in disease epidemiology, and development prioritization fueled the successful development of two different polio vaccines and the near eradication of a feared disease. Science has developed in an extraordinary fashion since the publication of 1985 IOM reports on vaccine development priorities (IOM, 1985a,b). These advances have occurred because of the development of molecular approaches to the cloning and characterization of virulence determinants of specific viral, bacterial, and parasitic organisms and because there is a better understanding of the cellular and molecular interactions that follow host responses to deliberate immunization or infection with a specific pathogen. This section presents a brief summary of some of the major scientific successes so that their contribution to the development of specific vaccines can be more fully appreciated.
It may be useful to describe the development of regulatory T cells by simply considering mature T cells that are recent emigrants from the thymus and are naïve (e.g., they have not yet encountered an antigen as precursor T-helper cells). Note that precursors of Th cells normally recognize foreign peptides in association with major histocompatability complex (MHC) class II on antigenpresenting cells (APCs) and express the α:β T-cell receptor with a CD3+, CD4+, CD8− phenotype. On the other hand, precursors of cytotoxic T lymphocytes (pCTLs) express the α:β TCR. These pCTLs usually recognize foreign peptide in the context of MHC class I on target cells and normally exhibit a CD3+ CD4−,