Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4-to 6-year-old children primed during infancy with DTaP (n ‫؍‬ 30) or DTwP (n ‫؍‬ 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (>50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically "high Th2 responders" as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.Morbidity and mortality to infectious diseases are maximal during early infancy, and as a consequence, the pressure to develop an increasingly broad range of vaccines in progressively younger age groups is increasing. An archetypal example is the diphtheria-tetanus-pertussis (DTP) vaccine, which provides protection against pathogens responsible for severe illness and death in millions of children worldwide, and initiatives to introduce versions of this and other vaccines for use in neonates to provide protection during the crucial first months of life are well advanced in many centers (3,11,17,29).The primary consideration underpinning research and development in this area continues to be that of safety, and the first major shift in formulation of the DTP vaccine from the original combination of whole-cell pertussis combined with tetanus and diphtheria toxoids (DTwP) to the new-generation acellular version (DTaP) was driven precisely by this imperative. Notably, the occurrence of febrile reactions in a small proportion of DTwPvaccinated children (6,8,13) which are likely to be associated with cell-mediated responses to the vaccine has provided the imp...

Infection with the helminthic parasites Ascaris lumbricoides and/or Necator americanus (hookworm) induces the production in man of high levels of serum IgE. The specificity of this IgE antibody when measured by RAST to a wide range of allergens was restricted in general to the helminthic antigens. Absorption of the sera with immunosorbents produced by coupling extracts of A. lumbricoides to CNBr activated Sepharose 4B established that Ascaris antigen specific IgE antibodies contributed a minor fraction of the total serum IgE. These observations suggest that parasitic infections in man as in laboratory animals potentiate the production of high levels of IgE with specificity unrelated to that of the parasite antigens. While the specificity of this potentiated IgE was not established, it is not directed towards inhalant allergens.