Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom

Abstract

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one-or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n ‫؍‬ 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of >8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of >8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.In November 1999, the United Kingdom introduced universal meningococcal C conjugate (MCC) vaccination at 2, 3, and 4 months of age, on the basis of safety and immunogenicity studies (15). A prelicensure study in 83 infants in the United Kingdom (18) who were given one of the three candidate MCC vaccines, a tetanus toxoid conjugate (MCC-TT) (14), at 2, 3, and 4 months of age demonstrated that the vaccine was highly immunogenic after a single dose at 2 months of age, with all infants achieving a putative protective antibody titer of Ն8 (bactericidal antibody levels in serum were measured with baby rabbit complement [rSBA]) (1a, 3). There was a further significant increase in antibody levels after a second dose of MCC-TT vaccine but no further increase after the third dose at 4 months of age. Antibody levels fell by 14 months of age, but booster antibody responses to meningococcal C polysaccharide and MCC vaccines provided evidence of successful priming for immunologic memory after the full course of three doses (18).The excellent response to this MCC-TT vaccine among infants at 2 months of age and the modest response to the third dose of vaccine raise the possibility that a one-or two-dose schedule in infants may be sufficient to provide protection from meningococcal C disease. Demonstration of priming for immune memory by the one-or two-dose schedules suggests that these regims could also provide long-term protection. This could be assessed by examining antibody responses to meningococcal C polysaccharide vaccination in the second year of life since children do not normally respond to polysaccharide ...

Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?

“…Following boosting, a lower SBA GMT was observed in the 2 dose priming group, with a GMT of 1538.0 (95%CI 1381.1-1712.6) compared to GMTs of 2472.1 (95%CI 2226.3-2745.0) and 1874.8 (95%CI 1684.4-2086.6) in the 4 month and 6 month groups. Lower SBA GMTs in the 2 dose priming group is consistent with data reported by Richmond et al, 5 and Borrow et al, 16 showing the quantity of antigen administered during priming correlates positively with post-primary SBA levels but negatively with the magnitude of the booster response. The reduced response in the 2 dose group may also be attributed to protein carrier-induced epitope suppression, with a dose dependent suppression of the antigen response.…”

Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom

“…NeisVac-C has also been reported to induce putative levels of protection in 92% of infants, with a GMT of 491 (95% CI, 275 to 877), when given at 2 months of age with a DTaP 3 /Hib-TT vaccine (Infanrix-Hib; GSK) though without concomitant PCV7 (26). A number of studies have reported good immunogenicity of a single dose of NeisVac-C when given in infancy with wP-containing vaccines (5,22).…”

Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT

“…23,27 The improved post-booster immunogenicity of fewer priming doses is well described for meningococcal C conjugate vaccines and is believed to be due to lower total antigen exposure favoring differentiation of B lymphoblasts into memory B cells instead of antibody-generating plasma cells. 14,15 In pneumococcal conjugate vaccines, a study of Fijian infants receiving 1 PCV7 priming dose followed by the 23-valent pneumococcal polysaccharide vaccine at 12 months had higher IgG GMCs for serotypes 4, 9V, and 19F compared with those who had been primed with 2 or 3 PCV7 doses. 13 Similarly, infants receiving a lower antigen-containing investigational tetravalent pneumococcal conjugate vaccine for priming had higher booster responses than those who had received the higher antigencontaining preparation.…”