infants receiving the PRP-OMP vaccine plus MMR were reported to develop irritability compared with 35 percent for groups receiving either vaccine alone, and a study by Ferreccio et al. (1991), which found a 7 to 20 percent increase in fever in children who received PRP-T with DPT than in those who received DPT alone.

Immunization with the first-generation Hib polysaccharide, or purified PRP, vaccine stimulates production of anti-PRP antibody in the same manner as natural infection (Granoff and Cares, 1985; Norden et al., 1976; Trollfors et al., 1992). This immune response is felt to be T-cell independent. In contrast, the immune responses to PRP conjugate vaccines appear to use T cells as well as B cells (Robbins and Schneerson, 1990; Steinhoff et al., 1991; Weinberg and Granoff, 1988). Antibodies produced in response to the intact organism, plain PRP vaccines, and conjugate vaccines have subtle differences, but all have been demonstrated to have in vitro opsonic and bactericidal activities and to be protective in animal models of Hib disease as well as in human trials (Adams, 1992; Anderson et al., 1972; Black, 1992; Black et al., 1988, 1991a,b; Cates, 1985; Cates et al., 1985; Eskola et al., 1987, 1990a,b, 1992; Fothergill and Wright, 1933; Fritzell and Plotkin, 1992; Gray, 1990; Kulhanjian, 1992; Loughlin et al., 1992; Musher et al., 1988; Newman et al., 1973; Peltola, 1992; Peltola et al., 1984; Robbins et al., 1973; Santosham et al., 1991b; Schneerson et al., 1971; Schreiber et al., 1986; Smith et al., 1989; Vadheim, 1992).

The difference in reliance on T cells for antibody production results in differences in the age at which the antibody response occurs, the amount of antibody produced, and the ability to boost antibody production by revaccination or exposure to the organism. The conjugate vaccines stimulate anti-PRP antibody responses in young infants, whereas the plain PRP vaccines do not provide protective amounts of antibody in most individuals until after the age of 2 years. The conjugate vaccines also induce larger amounts of anti-PRP antibodies in vaccinees of all ages, and they induce an anti-PRP antibody response in many individuals who do not respond well to natural infection with Hib or to the plain PRP vaccine, including patients with Hib disease before the age of 2 years and those with splenectomy; sickle cell disease; malignancy; IgG2 deficiency; Navajo, Apache, and Alaskan natives; and allogeneic bone marrow recipients (Barra et al., 1992; Edwards et al., 1989; Feldman et al., 1990; Frank et al., 1988; Gigliotti et al., 1989, 1991; Granoff et al., 1989; Kafidi and Rotschafer, 1988; Kaplan et al., 1988; Marcinak et al., 1991; Rubin et al., 1989, 1992; Santosham et al., 1992; Siber et al., 1990; Steinhoff et al., 1991; Walter et al., 1990; Weinberg and Granoff, 1990; Weisman et al., 1987).

It is evident that the different Hib vaccines produce not only different quantities of anti-PRP antibody but also that this antibody differs in such characteristics as IgG subclass, avidity, and affinity (Ambrosino et al., 1992;



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