antibodies to equilibrate with the circulating IgG pool and be transported across the placenta. For tetanus toxoid the optimal timing for immunization of a pregnant woman to achieve neonatal protection is 60 days before delivery (or at least 20 days after administration of the second dose) (Chen et al., 1983). The ideal vaccine should induce high maternal levels of IgGl antibodies; the maximum response should occur after the administration of one dose, reaching its peak within 2 weeks of immunization; and protective levels should persist for several years, providing protection in subsequent pregnancies. For most vaccines, the vaccine would be given early in the third trimester (28 to 32 weeks of gestation), a time when organogenesis is complete and when most events associated with adverse pregnancy outcomes are past. Theoretically, this timing would also provide protection for many prematurely born infants.

For some diseases for which immunization of the pregnant woman has been proposed (e.g., neonatal and pregnancy-related GBS infections), active immunization of the infant would be unnecessary because susceptibility is limited to young infants, pregnant women, and adults with either defined underlying medical conditions or advanced age. For others, such as Hib and RSV infections, active immunization would also be required. Maternal antibody can interfere with infant responses to live-virus vaccines, but this has not been demonstrated for inactivated viral vaccines, such as influenza virus vaccine, or for bacterial antigens, including tetanus toxoid, serogroup A and C meningococcal polysaccharides, or Hib polysaccharide (Insel et al., 1994). While the issue of suppression, activation or priming, or alteration of the repertoire of antibody responses in the infant should be studied as vaccines are developed, the evidence to date is reassuring.

As mentioned above, several of the vaccines recommended for accelerated development in the 1985 IOM report have been licensed for use, and several vaccines now in the development pipeline were not even contemplated in 1985. Rapid advances in the biomedical sciences and new knowledge about disease etiology and epidemiology can quickly change priorities. Before reviewing some of the major biomedical advances that are allowing vaccine development to proceed in ways not previously imagined, it will be useful to take a look at one of the vaccine successes known to all—the development of polio vaccines and the near eradication of a dreaded disease.

Poliomyelitis was a relatively insignificant disease in the United States before 1900, when epidemics of increasing severity began to appear in different parts of the country. The average annual incidence of the disease for the years