Haemophilus influenzaeType B (Hib) Antibody Responses in Children Given Diphtheria‐Tetanus–Acellular Pertussis–Hib Combination Vaccines

To the Editor—Goldblatt et al. [1] reported that the individual responses to the different vaccine antigens among a group of infants given a diphtheria-tetanus toxoid–acellular pertussis toxin–Haemophilus influenzae type b (DTaP-Hib) conjugate (polyribosylribitol phosphate–tetanus toxoid [PRP-T]) combination vaccine were positively correlated, so that infants with a high antibody response to 1 antigen tended to have a high response to the others and vice versa. They speculate that this may reflect individual variation in the degree of age-dependent maturation of the immune system. We studied 2 cohorts of infants in successive years; the first was given diphtheria-tetanus toxoid–pertussis toxin (DTP)-Hib vaccine containing whole-cell pertussis toxin (DTwP-Hib vaccine) [2], and the second was given DTaP-Hib vaccine containing a 2-component pertussis vaccine (Aventis Pasteur, Lyon, France) [3, 4]. In both series, the Hib vaccine was a tetanus conjugate (PRP-T; Pasteur Mérieux), and doses of tetanus and diphtheria toxoids were identical. Like Goldblatt and colleagues, we observed positive correlations between the responses to PRP and other vaccine antigens in both groups (table 1), and, like them, we noted a closer correlation between the anti-PRP response and the anti-tetanus response than between other antigen pairs, which was statistically significant in both series. This difference was particularly marked in the DTwPHib group. However, we question the explanation of this phenomenon proposed by Goldblatt et al. [1]. The tendency to find positive correlations for responses to nearly all antigen pairs supports the idea of a “general” ability to respond, which varies in size consistently for all antigens from one individual to another, but this cannot explain the closer relationship between the responses to the 2 tetanus toxoid–containing vaccine components. Dagan and colleagues [5] have also reported a significant positive correlation between anti-PRP and anti-tetanus responses in mixing studies involving DTwP-Hib combinations containing PRP-T, and they failed to show any significant correlation between anti-Hib and anti-diphtheria responses. They offer several hypothetical immunological mechanisms to explain their observations [5]. The variety and unpredictability of mixing effects observed to date in clinical studies involving protein-polysaccharide conjugate vaccines [6] suggest that a single, simple explanation will not emerge and that physicochemical, demographic, age, and dose-regimen effects may all be operating. However, the consistent observation of a positive correlation in the size of individuals’ antibody responses to these related antigens, together with a reduction in response to both Hib and tetanus components when DTP and PRP-T vaccines are combined in the same syringe [7–10], suggests that an antigen-specific immunological mechanism is also operating. The positive correlation between tetanus and Hib antibody responses argues against carrier-induced epitopic suppression operating through competition between antigens [6], but it may instead reflect variation in the efficacy of T cell help when related antigens are combined at the same injection site.