To test for immunologic memory after a single dose of meningococcal C conjugate (MCC) vaccine in toddlers, 226 children 12-18 months old were randomized to receive 1 of 3 MCC vaccines, with a C polysaccharide booster 6 months later. The protein conjugate was diphtheria mutant toxoid in 2 vaccines (MCC-CRM(197)) and was tetanus toxoid in the third (MCC-TT). One month after the MCC vaccines, 91%-100% of children had serum bactericidal antibody (SBA) titers > or =8, and 89%-100% had a > or =4-fold increase. Geometric mean titer (GMT) increased from <4 to 215 (95% confidence interval [CI], 166-279). MCC-TT induced higher SBA GMTs (P<.001) and higher proportions with SBA > or =8 (P=.02) than did the MCC-CRM(197) vaccines. By 6 months, GMTs had decreased to 55.1 (95% CI, 40-76), but IgG antibody avidity increased (P<.001). Induction of immunologic memory was confirmed by a GMT of 1977 (range, 1535-2547) after the polysaccharide booster and a further increase in avidity. This evidence justified the use of a single dose in a catch-up immunization program for children 1-18 years old.
In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM 197 ) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n ؍ 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM 197 or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM 197 vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.In November 1999, the United Kingdom introduced conjugate vaccines against meningococcal serogroup C disease (MCC vaccines) into its immunization schedule for infants, with promising early reports of efficacy (18). The vaccines were also offered to all children between 1 and 17 years of age as a catch-up program that started in November 1999 and was completed within a year. The evidence of safety and immunogenicity of the MCC vaccines in these age groups was obtained from phase II trials conducted in the United Kingdom and sponsored by the Department of Health. Following promising results of early trials using the 2-, 3-, and 4-month schedule in United Kingdom infants (16), the Department of Health sponsored a comprehensive clinical trials program to evaluate the performance of candidate MCC vaccines in toddlers, children starting school, children leaving school, and young adults (12).One concern was the potential for interaction between the MCC vaccines, which contained either tetanus toxoid (TT) or the CRM 197 derivative of diphtheria toxin as the protein carrier, and the diphtheria and tetanus vaccines given as booster doses at school entry (DT) or school leaving (Td). To address these concerns, trials were conducted in which children received MCC vaccine a month before or after, or at the same time as, their DT or Td booster vaccine. Humoral immune responses against DT and MCC antigens were assessed following each vaccination.Since it was anticipated that licensure of the MCC vaccines would be based on immunogenic...
SummaryThere are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count < 300 cells/ml). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-g secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98·2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-g spots to CD4 T cell count ratio was > 1·5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immunedeficient HIV-1 patients. A combination of TB antigen-specific IFN-g responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.
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